The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
Enhancement of viral infectivity caused by non-neutralizing antibodies. There are at least two mechanisms known to account for this: mediation by Fc receptors (RECEPTORS, FC) or by complement receptors (RECEPTORS, COMPLEMENT). Either the virus is complexed with antiviral IMMUNOGLOBULIN G and binds to Fc receptors, or virus is coated with antiviral IMMUNOGLOBULIN M and binds to complement receptors.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
Antibodies produced by a single clone of cells.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.
Immunoglobulins produced in response to VIRAL ANTIGENS.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Established cell cultures that have the potential to propagate indefinitely.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.
A cell line derived from cultured tumor cells.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells.
A calcium-dependent pore-forming protein synthesized in cytolytic LYMPHOCYTES and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell.
A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A 46-kD stimulatory receptor found on resting and activated NATURAL KILLER CELLS. It has specificity for VIRAL HEMAGGLUTININS that are expressed on infected cells.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
An activating NK cell lectin-like receptor subfamily that regulates immune responses to INFECTION and NEOPLASMS. Members of this subfamily generally occur as homodimers.
Receptors that are specifically found on the surface of NATURAL KILLER CELLS. They play an important role in regulating the cellular component of INNATE IMMUNITY.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
Proteins prepared by recombinant DNA technology.
Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.
Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.
A 30 kDa stimulatory receptor found on resting and activated NATURAL KILLER CELLS.
Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors.
An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.
Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).
Glycoproteins found on the membrane or surface of cells.
Proteins secreted from an organism which form membrane-spanning pores in target cells to destroy them. This is in contrast to PORINS and MEMBRANE TRANSPORT PROTEINS that function within the synthesizing organism and COMPLEMENT immune proteins. These pore forming cytotoxic proteins are a form of primitive cellular defense which are also found in human LYMPHOCYTES.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Sites on an antigen that interact with specific antibodies.
Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.
The 140 kDa isoform of NCAM (neural cell adhesion molecule) containing a transmembrane domain and short cytoplasmic tail. It is expressed by all lymphocytes mediating non-MHC restricted cytotoxicity and is present on some neural tissues and tumors.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.

Early membrane rupture events during neutrophil-mediated antibody-dependent tumor cell cytolysis. (1/1442)

Although cell-mediated cytolysis is a fundamental immune effector response, its mechanism remains poorly understood at the cellular level. In this report, we image for the first time transient ruptures, as inferred by cytoplasmic marker release, in tumor cell membranes during Ab-dependent cellular cytolysis. The cytosol of IgG-opsonized YAC tumor cells was labeled with tetra-methylrhodamine diacetate followed by the formation of tumor cell-neutrophil conjugates. We hypothesized that tumor cell cytolysis proceeds via a series of discrete membrane rupture/resealing events that contribute to marker release. To test this hypothesis, we occluded the fluorescence image of the labeled tumor cells by passing an opaque disk into a field-conjugated plane between the light source and the sample. Multiple small bursts of fluorescent label release from tumor cells could be detected using a photomultiplier tube. Similarly, multiple fluorescent plumes were observed at various sites around the perimeter of a target. These findings support a multihit model of target cytolysis and suggest that cytolytic release is not focused at specific sites. Cytolytic bursts were generally observed at 20-s intervals, which match the previously described reduced nicotinamide-adenine dinucleotide phosphate and superoxide release oscillation periods for neutrophils; we speculate that metabolic oscillations of the effector cell drive the membrane damage of the target.  (+info)

Cytotoxicity of human and baboon mononuclear phagocytes against schistosomula in vitro: induction by immune complexes containing IgE and Schistosoma mansoni antigens. (2/1442)

Normal human blood monocytes, pre-incubated at 37 degrees C with sera from patients infected with Schistosoma mansoni, strongly adhered to S. mansoni schistosomula in vitro, whereas no significant adherence was induced by sera from uninfected individuals. Comparable adherence occurred with normal baboon blood monocytes or peritoneal macrophages when these cells were incubated with sera from S. mansoni-infected baboons. Adherence of macrophages to schistosomula was associated with damage to the larvae, as estimated by a 51Cr release technique. Neither adherence nor cytotoxicity was induced by pre-incubation of the schistosomula, instead of the monocytes, with immune serum. The relevant factor in immune serum was heat-labile, but was not a complement component. Absorption and ultracentrifugation experiments showed that immune complexes, containing S. mansoni-specific IgE antibody and soluble parasite antigens, produced monocyte or macrophage adherence and cytotoxicity. Similar observations have been reported previously in the rat model. Since the production of large amounts of IgE is a predominant feature of schistosome infections in man and experimental animals, it is possible that this new mode of mononuclear phagocyte activation could act as an immune effector mechanism against S. mansoni.  (+info)

Improving the efficacy of antibody-interleukin 2 fusion proteins by reducing their interaction with Fc receptors. (3/1442)

Fusion proteins between whole antibodies (Abs) and cytokines (immunocytokines) such as interleukin 2 have shown efficacy in several mouse tumor models despite a circulating half-life that is significantly shorter than that of the original Ab. We have examined the potential mechanisms responsible for clearance and shown that an important factor is enhanced binding to Fc receptor (FcR). Improvements in the half-lives of two different immunocytokines were made by changing the isotype of the human heavy chain C region from IgG1 or IgG3 to those with reduced binding to FcR, e.g., IgG4. The same effect could also be achieved through site-directed mutagenesis of the FcR binding site in the IgG1 H chain. In vitro studies using mouse J774 FcR-expressing cells showed increased binding of interleukin 2-based immunocytokines, relative to their corresponding Abs, and that this was reversed in those fusion proteins made with IgG4 or mutated IgG1 H chains. All of the fusion proteins showing reduced FcR binding also had reduced Ab-dependent cellular cytotoxicity activity, as measured in 4-h chromium release assays. A complete loss of complement-dependent cytotoxicity activity was seen with an IgG4-based immunocytokine derived from an IgG1 Ab with potent activity. Despite these reduced effector functions, the IgG4-based immunocytokines with extended circulating half-lives showed equivalent (in the case of severe combined immunodeficiency mouse xenograft models) or better (in the case of syngeneic models) efficacy in mouse tumor models than the original IgG1-based molecules. These novel immunocytokines may show improved efficacy in therapeutic situations where T cell- rather than natural killer- or complement-mediated antitumor mechanisms are involved.  (+info)

Monoclonal Lym-1 antibody-dependent cytolysis by neutrophils exposed to granulocyte-macrophage colony-stimulating factor: intervention of FcgammaRII (CD32), CD11b-CD18 integrins, and CD66b glycoproteins. (4/1442)

Murine monoclonal antibody (MoAb) Lym-1 is an IgG2a able to bind HLA-DR variants on malignant B cells and suitable for serotherapeutic approaches in B-lymphoma patients. We have previously shown that Lym-1 can synergize with granulocyte-macrophage colony-stimulating factor (GM-CSF) to trigger neutrophil cytolysis towards Raji cells used as a model of B-lymphoma targets. Here we provide evidence for the intervention of certain neutrophil receptors or surface molecules in this model of cell-mediated lysis. The lysis was completely inhibited by the anti-FcgammaRII MoAb IV.3 and unaffected by the anti-FcgammaRIII MoAb 3G8. This suggests that neutrophil cytolysis involves FcgammaRII without cooperation of this receptor with FcgammaRIII. Moreover, the lysis was inhibited by an anti-CD18 MoAb (MEM48) and by a MoAb specific for carcinoembryonic antigen (CEA)-like and glycophosphatidyl inositol (GPI)-linked glycoproteins (CD66b). Using an immunofluorescence staining procedure, cross-linking of CD66b induced the redistribution of CD11b on neutrophils with distinct areas of CD11b clustering via a process susceptible of inhibition by D-mannose. This is consistent with the ability of CD11b-CD18 and CD66b to undergo lectin-like physical interactions on the neutrophil surface. Such a type of interaction is presumably instrumental for neutrophil cytolytic activity in that the lysis was inhibited by D-mannose and enhanced by the MoAb VIM-12, which mimics the cooperation between CD11b and GPI-anchored molecules by specifically interacting with CD11b lectin-like sites. Therefore, the present results prove the absolute requirement for FcgammaRII in neutrophil GM-CSF/Lym-1-mediated cytolysis and, on the other hand, define the crucial role of CD66b and CD11b/CD18 in the expression of the cell lytic potential.  (+info)

Natural cytotoxic and antibody-dependent cellular cytotoxic activity of cells in the decidua basales and metrial glands of pseudopregnant rats with deciduomata. (5/1442)

Cytotoxic cells are present in the uterine wall of pregnant rats. To determine if the cytotoxic activity arises in response to semen or the products of conception, the profile of cytotoxic activity in deciduomata of pseudopregnant rats was examined. To examine NK activity, Yac-1 cells were used as targets in chromium release cytotoxicity assays and an antibody to Yac-1 cells was included in some assays to determine antibody-dependent cellular cytotoxic (ADCC) activity. Cells from the metrial glands and deciduae of deciduomata of rats at days 10 and 13 of pseudopregnancy did not show NK activity but ADCC activity was present. To examine natural cytotoxic (NC) activity, Wehi 164 cells were used as targets in chromium release cytotoxicity assays. Cells isolated from the metrial glands and deciduae of rats at day 10 of pseudopregnancy were able to kill Wehi 164 cells after 21 h assays, thus demonstrating NC activity. The profile of cytotoxic activity in the uterine wall of pseudopregnant rats with deciduomata is similar to that found in pregnancy and is thus independent of semen or the products of conception.  (+info)

Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity. (6/1442)

In addition to their role in peptide antigen presentation, class I MHC proteins also play a critical role in inhibiting natural killer (NK) cytotoxicity through interaction with NK inhibitory receptors. Thus, NK cells are cytotoxic to virus-infected and tumor cells that have lost class I MHC protein expression. However, the nature of the receptors involved in the triggering of lysis of target cells is poorly understood. CD16 (Fcgamma receptor III) has been described as a receptor expressed on NK cells that facilitates antibody-dependent cellular cytotoxicity (ADCC) by binding to the Fc portion of various antibodies. However, we show here that CD16 has a broader function and is directly involved in the lysis of some virus-infected cells and tumor cells, independent of antibody binding. The presence of a putative CD16 ligand on appropriate target cells has also been demonstrated by the use of a CD16-Ig fusion protein.  (+info)

C-myc antisense oligodeoxynucleotides can induce apoptosis and down-regulate Fas expression in rheumatoid synoviocytes. (7/1442)

OBJECTIVE: To investigate the role of c-myc in the pathogenesis of rheumatoid arthritis (RA) and the mechanism of synovial apoptosis. METHODS: Using cultured human synoviocytes from patients with RA and c-myc antisense oligodeoxynucleotides (AS ODN), we examined the inhibition of cell proliferation by the MTT assay and the induction of apoptosis with TUNEL staining and fluorescence microscopy. In addition, the effect of c-myc on down-regulation of Fas expression was analyzed by flow cytometry, cytotoxicity assay, and reverse transcriptase-polymerase chain reaction. RESULTS: Treatment with c-myc AS ODN induced inhibition of cell proliferation, along with down-regulation of c-Myc protein and c-myc messenger RNA (mRNA) expression. The morphologic changes of synovial cell death were typical of apoptosis. In addition, c-myc AS ODN treatment down-regulated expression of Fas mRNA but not Fas antigen. Analysis of the involvement of the caspase cascade revealed that the cytotoxic activity of c-myc AS ODN was completely blocked by inhibitors of both caspase 1 (YVAD-FMK) and caspase 3 (DEVD-FMK). CONCLUSION: Our results strongly suggest that c-myc AS ODN might be a useful therapeutic tool in RA and clarify that cell death by c-myc AS ODN is induced through the caspase cascade, similar to Fas-induced apoptosis. In addition, combination therapy with anti-Fas antibody and c-myc AS ODN reduced Fas-dependent cytotoxicity.  (+info)

Differential involvement of the CD95 (Fas/APO-1) receptor/ligand system on apoptosis induced by the wild-type p53 gene transfer in human cancer cells. (8/1442)

The CD95 (Fas/APO-1) system regulates a number of physiological and pathological processes of cell death. The ligand for CD95 induces apoptosis in sensitive target cells by interacting with a transmembrane cell surface CD95 receptor. We previously reported that the recombinant adenovirus-mediated transfer of the wild-type p53 gene caused apoptotic cell death in a variety of human cancer cells. To better understand the mechanism responsible for this cell death signaling, we have investigated the potential involvement of the CD95 receptor/ligand system in p53-mediated apoptosis. The transient expression of the wild-type p53 gene upregulated the CD95 ligand mRNA as well as protein expression in H1299 human lung cancer cells deficient for p53 and in DLD-1 and SW620 human colon cancer cells with mutated p53, all of which constitutively expressed CD95 receptor as shown by a flow cytometric analysis, and induced rapid apoptotic cell death as early as 24 h after gene transfer. However, the sensitivity to the cytolytic effect of agonistic anti-CD95 antibody (CH11) varied among these cell lines: CH11 induced apoptosis in H1299 cells, but not in DLD-1 and SW620 cells despite their abundant CD95 receptor expression, suggesting that the CD95 receptors on DLD-1 and SW620 cells might be inactivated. In addition, an antagonistic anti-CD95 ligand antibody (4H9) that interfered with the CD95-receptor-ligand interaction partially reduced the apoptosis induced by the wild-type p53 gene transfer in H1299 cells, whereas apoptosis of DLD-1 and SW620 cells occurred in the presence of 4H9. Taken together, these findings led us to conclude that the CD95 receptor/ligand system is differentially involved in p53-mediated apoptosis, suggesting that the restoration of the wild-type p53 function may mediate apoptosis through CD95 receptor/ligand interactions as well as an alternative pathway.  (+info)

Looking for antibody-dependent cell-mediated cytotoxicity? Find out information about antibody-dependent cell-mediated cytotoxicity. An immunologic response in which an immunologic effector cell binds to a target cell coated with antibodies, triggering a series of metabolic events that... Explanation of antibody-dependent cell-mediated cytotoxicity
TY - JOUR. T1 - HIV-1 gp120-Specific Antibody-Dependent Cell-Mediated Cytotoxicity Correlates with Rate of Disease Progression. AU - Baum, Linda L.. AU - Cassutt, Kelly J.. AU - Knigge, Kevin. AU - Khattri, Roli. AU - Margolick, Joseph. AU - Rinaldo, Charles. AU - Kleeberger, Cynthia A.. AU - Nishanian, Parunag. AU - Henrard, Denis R.. AU - Phair, John. PY - 1996/9/1. Y1 - 1996/9/1. N2 - The Ab-dependent cell-mediated cytotoxicity (ADCC) activity of anti-gp120 Abs in serum from four groups of HIV-1-positive individuals in the Multicenter AIDS Cohort Study was evaluated at several time points over a 10-yr period. HIV-1-positive individuals who progressed to AIDS within 3 yr of seroconversion (rapid progressors) were compared with seroconverters who did not progress to AIDS within 6 yr (nonrapid progressors) and individuals who were seropositive when they entered the study and did not progress to AIDS within 9-10 yr (nonprogressors). At the visit closest to AIDS, rapid progressors had ...
HIV-1-particular antibody-dependent cellular cytotoxicity (ADCC) antibodies within HIV-1-positive (HIV-1+) individuals predominantly target CD4-induced (CD4i) epitopes on HIV-1 envelope glycoprotein (Env). various stages of downregulating CD4, were all susceptible to NK cell-mediated ADCC. Importantly, we PCDH9 observed that this cytolysis of bystander cells and early infected cells in this culture system was driven by sensitization of target cells by inoculum-derived HIV-1 Env or virions. This phenomenon provided Env to target cells prior to Env expression, resulting in artifactual ADCC measurements. Future studies should take into consideration the inherent caveats of contamination systems and develop improved models to address the potential role for ADCC against cells with nascent HIV-1 contamination. IMPORTANCE An increasing body of evidence suggests that ADCC contributes to protection against HIV-1 acquisition and slower HIV-1 disease progression. Targeting cells early through the infection ...
The antibody-dependent cell-mediated cytotoxicity (ADCC), also referred to as antibody-dependent cellular cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose membrane-surface antigens have been bound by specific antibodies. It is one of the mechanisms through which antibodies, as part of the humoral immune response, can act to limit and contain infection. ADCC is independent of the immune complement system that also lyses targets but does not require any other cell. ADCC requires an effector cell which classically is known to be natural killer (NK) cells that typically interact with IgG antibodies. However, macrophages, neutrophils and eosinophils can also mediate ADCC, such as eosinophils killing certain parasitic worms known as helminths via IgE antibodies. ADCC is part of the adaptive immune response due to its dependence on a prior antibody response. The coating of target cells with antibodies is ...
INDICATIONS. Septilin is an immunomodulatory and anti-inflammatory herbal formulation, which strengthen the immune responses of the body. Septilin stimulates phagocytosis by macrophage activation and increases the polymorphonuclear cells and helps overcome infection. It builds up resistance to disease and helps prevent reinfection, augments granulocyte-macrophage differentiation, natural killer cell activity and antibody-dependent cell cytotoxicity. Septilins stimulatory effect on the humoral immunity increases the antibody forming cells, thereby enhancing the secretion of antibodies into the circulation. Septilin also augments the population of erythropoietic and granulopoietic precursor cells, stab cells and primary.. INSTRUCTIONS Take 1 or 2 pills twice daily, preferably with meals. Allow several weeks for full benefit. The use of natural products provides progressive but long-lasting results.. If you miss a dose of this medicine and you are using it regularly, take it as soon as possible. ...
INDICATIONS. Septilin is an immunomodulatory and anti-inflammatory herbal formulation, which strengthen the immune responses of the body. Septilin stimulates phagocytosis by macrophage activation and increases the polymorphonuclear cells and helps overcome infection. It builds up resistance to disease and helps prevent reinfection, augments granulocyte-macrophage differentiation, natural killer cell activity and antibody-dependent cell cytotoxicity. Septilins stimulatory effect on the humoral immunity increases the antibody forming cells, thereby enhancing the secretion of antibodies into the circulation. Septilin also augments the population of erythropoietic and granulopoietic precursor cells, stab cells and primary.. INSTRUCTIONS Take 1 or 2 pills twice daily, preferably with meals. Allow several weeks for full benefit. The use of natural products provides progressive but long-lasting results.. If you miss a dose of this medicine and you are using it regularly, take it as soon as possible. ...
Lymphocytes T Cytotoxiques 0 questions Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from natural killer cells (KILLER CELLS, NATURAL) and from KILLER CELLS mediating antibody-dependent cell cytotoxicity. There are two effector phenotypes: TC1 and TC2. ...
Most therapies for autoimmune and inflammatory diseases either neutralize or suppress production of inflammatory cytokines produced by activated macrophages (e.g., TNFα, IL-1, IL-6, IL-17, GM-CSF). However, no approved therapies directly target this activated subset of macrophages. First, we undertook to examine whether the folate receptor beta (FR-β) positive subpopulation of macrophages, which marks the inflammatory subset in animal models of rheumatoid arthritis, might constitute the prominent population of macrophages in inflamed lesions in humans. Next, we utilized anti-FR-β monoclonal antibodies capable of mediating antibody-dependent cell cytotoxicity (ADCC) to treat animal models of rheumatoid arthritis and peritonitis. Human tissue samples of rheumatoid arthritis, Crohns disease, ulcerative colitis, idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, chronic obstructive pulmonary disease, systemic lupus erythematosus, psoriasis, and scleroderma are all characterized by
Antibody‐dependent cell‐mediated cytotoxicity (ADCC) is an immunologic cytotoxic effector mechanism that is dependent on the cooperative interaction of humoral and cellular effector elements
TY - JOUR. T1 - Immune components of the intestinal mucosae of ageing and protein deficient mice. AU - Lim, T. S.. AU - Messiha, N.. AU - Watson, R. R.. PY - 1981/1/1. Y1 - 1981/1/1. N2 - The studies were designed to investigate the effect of ageing and low protein (4%) diet on antibody-dependent cell-mediated cytotoxicity (ADCC) and IgA concentration in the intestine. Both ADCC activity and IgA concentration were shown to reach mature levels at 17 weeks old. The effect of ageing was greater on ADCC activity which showed a drastic drop in activity at 75 weeks old than IgA which had only a slight decline in concentration at this age. The low protein diet has a greater suppressive effect on IgA concentration than on ADCC activity. As the duration of feeding low protein to the young mice increased, greater decline in IgA concentration in the intestine was observed. There was, however, no significant difference from the normal mice in ADCC activity and IgA concentration of aged and adult mice given ...
The immune system contains many mechanisms for the identification and attack of unwanted cells (e.g. viral infection, tumors, etc.). Amongst these are Antibody Dependent Cellular Cytotoxicity (ADCC ) and Complement Dependent Cytotoxicity (CDC). In both cases, the cellular killing is mediated by an antibody binding to its target on the cell surface. In the case of ADCC, the killing is mediated by natural killer (NK) cells, while in the case of CDC activity, the killing is mediated by complement proteins. In both cases, Aragen has significant experience with a broad diversity of target cells and mechanisms of killing.. For ADCC assays, Aragen typically utilizes IL-2 activated normal PBMCs as effector cells and a variety of tumor cells as target cells. However, various sources of PBMCs (e.g normal vs diseased donors) can also be sourced. Aragens preferred readout for this assay is a FACS-based method, although alternative methods (e.g. ATP release) can also be used.. For CDC, these assays are ...
TY - JOUR. T1 - Regulation of IgG antibody-dependent cellular cytotoxicity in vitro by IgM antibodies. Mechanism and characterization of effector lymphocytes. AU - Perlmann, H.. AU - Perlmann, P.. AU - Moretta, L.. AU - Ronnholm, M.. PY - 1981. Y1 - 1981. N2 - IgM antibodies have previously been reported to either inhibit or induce antibody-dependent lymphocyte cytotoxicity (ADCC). Here the authors show that human lymphocytes lyse bovine erythrocytes (Eb) in the presence of either IgM or IgG anti-Eb from rabbits. Seven out of 20 IgM preparations (Sephadex G-200) were ADCC-active. IgG-dependent ADCC was inhibited by human IgG but not by IgM. In contrast, IgM ADCC was inhibited by both IgG and IgM. The effector cells in IgM ADCC were a subpopulation of lymphocytes with distinct Fc receptors for both IgG and IgM. Most of them also had sheep erythrocyte receptors. Extensive purification of the ADCC-active IgM antibody preparations indicated that very small amounts of contaminating IgG anti-Eb were ...
TY - JOUR. T1 - Antibody-dependent cellular cytotoxicity mediated by murine lymphocytes activated in recombinant interleukin 2. AU - Shiloni, E.. AU - Eisenthal, A.. AU - Sachs, D.. AU - Rosenberg, S. A.. PY - 1987/1/1. Y1 - 1987/1/1. N2 - The incubation of murine splenocytes in recombinant interleukin 2 (RIL 2) gives rise to lymphokine-activated killer (LAK) cells that can lyse fresh, NK-resistant tumor cells but not normal cells in 4-hr 51Cr-release assays. Lysis by this IL 2-activated cell population was enhanced up to 100-fold by prior reaction of target cells with specific antisera reactive with antigens on the target cells. This antibody-dependent cellular cytoxicity (ADCC) also resulted in lysis of fresh normal target cells, which are not usually susceptible to LAK lysis. The ADCC was evident after 24 hr of incubation of splenocytes in RIL 2, but peak lytic activity was reached after 3 to 4 days of incubation. The concentrations of RIL 2 needed for the in vitro activation of the effectors ...
HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cellular-mediated cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to avoid the exposure of Env ADCC epitopes by downregulating CD4 and by limiting the overall amount of Env on the cell surface. In HIV-1, substitution of large residues such as histidine or tryptophan for serine 375 (S375H/W) in the gp120 Phe 43 cavity, where Phe 43 of CD4 contacts gp120, results in the spontaneous sampling of an Env conformation closer to the CD4-bound state. While residue S375 is well conserved in the majority of group M HIV-1 isolates, CRF01_AE strains have a naturally occurring histidine at this position (H375). Interestingly, CRF01_AE is the predominant circulating strain in Thailand, where the RV144 trial took place. In this trial, which resulted in a modest degree of protection, ADCC responses were identified as being part of the ...
Immunohistochemical analysis showed that FG88.2 glyco-epitopes were overexpressed on a broad range of tumour types with limited cross reactivity with normal human tissues. Characterisation of effector functions of FG88 and FG2811.72 mAbs demonstrated that they were capable of inducing potent antibody dependent cellular cytotoxicity (ADCC; EC50 FG88 mAbs: 10-9 M; EC50 FG2811.72 mAb: 10-10 M) and complement dependent cytotoxicity (CDC; EC50 FG88 mAbs: 10-9 M; EC50 FG2811.72 mAb: 10-9 M). In addition, FG88 mAbs were capable of inducing direct tumour cell death via oncosis which induces pore formation and lysis of tumour cells. Preliminary results showed that FG2811.72 mAb inhibited tumour cell growth in the absence of immune cells and complement proteins, but the mechanism of tumour cell growth inhibition remains unexplored. The excellent in vitro cytotoxicity of FG88 mAbs translated into potent anti-tumour efficacy and significant survival improvement in a colorectal hepatic metastasis xenograft ...
Second, a monoclonal antibody is developed to bind both MR1 and its own tumor-specific antigens to induce antibody-dependent cytotoxicity. improve the possibility of general pan-cancer immunotherapies that are reliant on tumor metabolites. or Salmonella enterica, or the MR1 ligand acetyl-6-FP [24]. These total outcomes indicate the fact that up to now unidentified ligand or ligands limited by MR1, and acknowledged by MR1T cells thus, have got an identical structure to other and Tropicamide acetyl-6-FP MAIT TCR ligands. Not only is it byproducts of glycolysis, methylglyoxal and glyoxal result from meals resources, however it really is tantalizing to take a position that MR1-expressing tumor cells go through elevated glycolysis to create methylglyoxal and glyoxal, which react with supplement B metabolites to create the antigen or antigens that bind MR1 and so are acknowledged by the TCRs of MR1T cells. As the unidentified metabolite antigens or antigen shown by MR1 are particular to or connected ...
Monoclonal antibodies against tumour cells mainly act via antibody dependent cellular cytotoxicity.. They also act via complement mediated lysis and by induction of apoptosis.. ...
Protection against disease-causing pathogens, known as immunity, involves numerous cells organs, tissues and their products. To able to understand the biology of immune cells (hematopoietic cells) and their role in an immune system, we have used several different methods, including transcriptome analyses, bioinformatics, production of recombinant proteins and analyses of some of them, focusing on the granule proteases by substrate phage display.. Hematopoietic cells express surface receptors interacting with the constant region of immunoglobulins (Igs) known as Fc receptors (FcRs). These receptors play major roles in the immune system, including enhancing phagocytosis, activating antibody dependent cellular cytotoxicity and cell activation. A detailed bioinformatics analysis of FcRs reveals that the poly-Ig receptors (PIGR), FcR-like molecules and common signalling γ chain all appeared very early with the appearance of the bony fishes, and thereby represent the first major evolutionary step in ...
Septilin possesses immune-modulatory and anti-inflammatory properties, which potentiate the non-specific immune responses of the body. Septilin stimulates phagocytosis by macrophage activation, increases the polymorphonuclear cells and helps overcome infection.Septilin builds up resistance to infection and helps prevent re-infection. Septilin augments granulocyte-macrophage differentiation, natural killer cell activity and antibody-dependent cytotoxicity.Septilins stimulatory effect on the humoral immunity increases the antibody-forming cells, thereby enhancing the secretion of antibodies into the circulation. Septilin also augments the synthesis of erythropoietic and granulopoietic precursor cells, stab cells and primary myelocytes.- Upper respiratory tract infections- Lower respiratory tract infections- Allergic disorders of upper respiratory tract- Skin and soft tissue infections and inflammations- Dental and periodontal infections- Infective and inflammatory conditions of the eye- Bone and joint
The role of antibody Fc-mediated effector functions in controlling or preventing infections by human immunodeficiency type 1 (HIV-1) and simian immunodeficiency (SIV) viruses has been recently highlighted in multiple studies. One of those effector functions, antibody-dependent cellular cytotoxicity …
The identification of EGFR as an oncogene has led to the development of anticancer therapeutics directed against EGFR (called EGFR inhibitors), including gefitinib,[21] erlotinib, afatinib, brigatinib and icotinib[22] for lung cancer, and cetuximab for colon cancer. More recently AstraZeneca has developed Osimertinib, a third generation tyrosine kinase inhibitor.[23] Many therapeutic approaches are aimed at the EGFR. Cetuximab and panitumumab are examples of monoclonal antibody inhibitors. However the former is of the IgG1 type, the latter of the IgG2 type; consequences on antibody-dependent cellular cytotoxicity can be quite different.[24] Other monoclonals in clinical development are zalutumumab, nimotuzumab, and matuzumab. The monoclonal antibodies block the extracellular ligand binding domain. With the binding site blocked, signal molecules can no longer attach there and activate the tyrosine kinase. Another method is using small molecules to inhibit the EGFR tyrosine kinase, which is on ...
Elotuzumab (Elo) is an IgG1 monoclonal antibody targeting SLAMF7 (CS1, CRACC, and CD319), which is highly expressed on multiple myeloma (MM) cells, natural killer (NK) cells, and subsets of other leukocytes. By engaging with FcγRIIIA (CD16), Elo promotes potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and macrophage-mediated antibody-dependent cellular phagocytosis (ADCP) toward SLAMF7+ MM tumor cells. Relapsed/refractory MM patients treated with the combination of Elo, lenalidomide, and dexamethasone have improved progression-free survival. We previously showed that Elo enhances NK cell activity via a costimulation mechanism, independent of CD16 binding. Here, we further studied the effect of Elo on cytotoxicity of CD16-negative NK-92 cells. Elo, but not other SLAMF7 antibodies, uniquely enhanced cytotoxicity mediated by CD16-negative NK-92 cells toward SLAMF7+ target cells. Furthermore, this CD16-independent enhancement of cytotoxicity required expression of SLAMF7 ...
Regulation of complement activity by immunoglobulin. I. Effect of immunoglobulin isotype on C4 uptake on antibody-sensitized sheep erythrocytes and solid phase immune complexes.
The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. RV144 secondary immune correlate analysis demonstrated that the combination of low plasma anti-HIV-1 Env IgA antibodies and high levels of antibody-dependent cellular cytotoxicity (ADCC) inversely correlate with infection risk. One hypothesis is that the observed protection in RV144 is partially due to ADCC-mediating antibodies. We found that the majority (73 to 90%) of a representative group of vaccinees displayed plasma ADCC activity, usually (96.2%) blocked by competition with the C1 region-specific A32 Fab fragment. Using memory B-cell cultures and antigen-specific B-cell sorting, we isolated 23 ADCC-mediating nonclonally related antibodies from 6 vaccine recipients. These antibodies targeted A32-blockable conformational epitopes (n = 19), a non-A32-blockable conformational epitope (n = 1), and the gp120 Env variable loops (n = 3). Fourteen antibodies mediated cross-clade target cell killing. ADCC-mediating ...
Background: Cetuximab is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) that prolongs survival in the treatment of head and neck cancer (HNC), but only in 10-20%. An immunological mechanism of action including natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) has been suggested. We investigated the effects of activating toll-like receptor (TLR)-8 to enhance activity of cetuximab-stimulated, FcγR bearing cells.. Objective: To determine the capability of TLR8-stimulation to enhance the activation and function of NK cells and dendritic cells (DC) in the presence of cetuximab-coated HNC cells.. Methods: Peripheral blood mononuclear cells (PBMC), NK, DC and CD8+ T cells were isolated and analyzed using 51Cr release ADCC, flow cytometry analysis, cytokine ELISA, and EGFR853-861 tetramer staining.. Results: TLR8 stimulation of unfractionated PBMC led to enhanced cetuximab-mediated ADCC in healthy donors (p=0.01) and HNC patients (p,0.05), ...
Twenty-two human leukaemias, comprising acute phase leucocytes from 13 acute myeloid and nine lymphoid leukaemias, were tested for susceptibility to spontaneous cell-mediated cytotoxicity (CMC) by untreated lymphocytes and lymphocytes treated for 18 h with 250 IU lymphoblastoid (Namalva) interferon (IFN-alpha). IFN-amplified killing (IAK) by lymphocytes from 24 normal lymphocyte donors was checked on the K562 erythroleukaemia cell line, for comparison with IAK on fresh leukaemias. Nine leukaemias were tested with lymphocytes from three donors, nine with lymphocytes from six donors, three with lymphocytes from nine donors, and one with lymphocytes from 11 donors. Some degree of susceptibility to IAK was found in five acute myeloid and five lymphoid leukaemias, which was markedly dependent upon the source of the effector lymphocytes and did not correlate with the degree of IAK on K562. The 12 other leukaemias were virtually resistant to IAK. The results emphasize the variability in the capacity of ...
HIV-1 Nef clones isolated from a rare subset of HIV-1-infected elite controllers (EC), with the ability to suppress viral load to undetectable levels in the absence of antiretroviral therapy, are unable to fully downregulate CD4 from the plasma membrane of CD4(+) T cells. Residual CD4 left at the plasma membrane allows Env-CD4 interaction, which leads to increased exposure of Env CD4-induced epitopes and increases susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). ADCC is mediated largely by natural killer (NK) cells, which control their activation status through the cumulative signals received through activating and inhibitory receptors. Recently, the activating NKG2D receptor was demonstrated to positively influence ADCC responses. Since HIV-1 Nef has been reported to reduce the expression of NKG2D ligands, we evaluated the relative abilities of Nef from EC and progressors to downmodulate NKG2D ligands. Furthermore, we assessed the impact of EC and progressor ...
These studies support our commitment to advancing the clinical development of genolimzumab (CBT-501) as an immuno-oncology therapy for many types of cancer. Based on these findings, a Phase 1 dose escalation and dose and disease expansion study will be initiated in the first half of 2017, said Gavin Choy, Pharm.D., Chief Operating Officer at CBT Pharmaceuticals.. Genolimzumab Injection (CBT-501). CBT-501 is a novel humanized IgG4 monoclonal antibody targeting the Programmed Death-1 (PD-1) membrane receptor on T lymphocytes and other cells of the immune system. CBT-501 has a comparable efficacy profile in in vitro and in vivo studies to marketed anti-PD-1 antibodies and has a superior safety profile with very low undesirable antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activity. The antibody (GB226) has been developed by Genor BioPharma Co. Ltd., a Walvax Company, who owns development and commercialization rights in China. CBT Pharmaceuticals, ...
Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here. ...
The depletion of CD19+ B cells by CD19-targeted CAR CD8+ T cells effectively eliminated autoantibody production and deferred or reversed disease manifestations of experimental lupus in two mouse models. These results contrast with previous results in the same mouse models, which showed resistance to anti-CD20 antibody-mediated B cell depletion (11-13). We propose that CD19-targeted CAR T cells have superior efficacy because cytotoxic T cells induce target cell death by a direct mechanism, whereas antibody-mediated cytotoxicity requires the buildup of bound antibody for complement-dependent target cell lysis, antibody-dependent cellular cytotoxicity, or clearance by phagocytes. Previous studies indicated that in models of lupus, the increased abundance of endogenous antibodies and immune complexes impairs B cell depletion by macrophages (12). Thus, anti-CD20 antibody was only effective if given repeatedly and at high doses to autoimmune mice. CD19-targeted CAR T cells, in contrast, kill B cells ...
Passive immunotherapies are intrinsically functional and include monoclonal antibodies, lymphocytes, and cytokines. Among these, antibody therapies are the most successful to date and treat a wide range of cancers. Antibodies are proteins produced by the immune system that bind to a target antigen on the cell surface. In normal physiology the immune system uses them to fight pathogens. Each antibody is specific to one or a few proteins. Those that bind to cancer antigens are used to treat cancer. Cell surface receptors are common targets for antibody therapies and include the CD20, CD274, and CD279. Once bound to a cancer antigen, antibodies can induce antibody-dependent cell-mediated cytotoxicity, activate the complement system, or prevent a receptor from interacting with its ligand, all of which can lead to cell death. Multiple antibodies are approved to treat cancer, including alemtuzumab, ipilimumab, nivolumab, ofatumumab, and rituximab ...
Background: Treatments that generate T cell-mediated immunity to a patients unique neoantigens are the current holy grail of cancer immunotherapy. In particular, treatments that do not require cumbersome and individualized ex vivo processing or manufacturing processes are especially sought after. Here we report that AGI-134, a glycolipid-like small molecule, can be used for coating tumor cells with the xenoantigen Galalpha1-3Galbeta1-4GlcNAc (alpha-Gal) in situ leading to opsonization with pre-existing natural anti-alpha-Gal antibodies (in short anti-Gal), which triggers immune cascades resulting in T cell mediated anti-tumor immunity. Methods: Various immunological effects of coating tumor cells with alpha-Gal via AGI-134 in vitro were measured by flow cytometry: (1) opsonization with anti-Gal and complement, (2) antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells, and (3) phagocytosis and antigen cross-presentation by antigen presenting cells (APCs). A viability kit was used to test AGI
Definition noun A type of T cell that does not express markers of either T orB-cell lineage, but may possess fc receptors for immunoglobulin g. It functions by killing target cell through antibody-dependent cell-mediated cytotoxicity or through perforin formation, killing cells without prior sensitization (hence, the name). ...
Introduction: Rituximab-CHOP (R-CHOP) remains the standard of care for patients with previously untreated DLBCL. Approximately 40% of patients are not cured with R-CHOP; thus, new therapies are needed. Obinutuzumab (GA101, G) is a glycoengineered type II anti-CD20 monoclonal antibody with improved direct cell death and antibody-dependent cell-mediated cytotoxicity compared to rituximab, and may have improved outcomes in certain patient subsets (Vitolo, ASH 2016). In addition, polatuzumab vedotin (pola) is an antibody drug conjugate (ADC) designed to deliver the potent microtubule inhibitor MMAE to cells expressing CD79b. Thus, pola has the potential to replace vincristine with a targeted agent (Tilly, ICML 2017). The dose escalation phase established a recommended phase 2 dose (RP2D) of pola at 1.8 mg/kg. We report updated results for this multicenter, open-label Phase Ib/II study of pola combined G-CHP at the RP2D (ClinicalTrials.gov NCT01992653). Methods: In the dose escalation phase of this ...
Petricevic B, Laengle J, Singer J, Sachet M, Singer J, Steger G, Bartsch R, Jensen-Jarolim E, Bergmann M. 2013. Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients. Journal of Translational Medicine. 11, 307 ...
Petricevic B, Laengle J, Singer J, Sachet M, Singer J, Steger G, Bartsch R, Jensen-Jarolim E, Bergmann M. 2013. Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients. Journal of Translational Medicine. 11, 307 ...
Epsilogen is a global leader in the development of immunoglobulin E (IgE) antibodies to treat cancer. IgE has several key features that make it ideal for the treatment of solid tumours including greater potency, enhanced tumour access and a long tissue half-life. The epsilon constant region of IgE binds very tightly to its cognate receptor (FcεRI) on the surface of immune effector cells including macrophages, monocytes, basophils and eosinophils. This interaction is up to 10,000 fold greater than the gamma chain of IgG has for its equivalent receptor and this results in the majority of IgE molecules being permanently attached to the surface of immune effector cells. The latter are therefore primed and ready to destroy cells expressing the antigen recognised by the IgE. As a result, IgE is able to permeate tissues more effectively than IgG and stimulate significantly greater levels of both ADCP (antibody-dependent cell-mediated phagocytosis) and ADCC (antibody-dependent cell-mediated ...
Ocrelizumab is a recombinant humanised monoclonal antibody that selectively targets CD20-expressing B cells. The precise mechanisms through which ocrelizumab exerts its therapeutic clinical effects in MS is presumed to involve immunomodulation through the reduction in the number and function of CD20-expressing B cells. Following cell surface binding, ocrelizumab selectively depletes CD20-expressing B cells through antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis. The capacity of B-cell reconstitution and preexisting humoral immunity are preserved.
Another mechanism by which mAbs have antitumor activity is through antibody-dependent cellular cytotoxicity (ADCC). To study the ADCC potential of HER2dMAb, we incubated OVCAR3 cells with or without peripheral blood mononuclear cells (PBMCs), in the presence of sera from HER2dMAb- or empty vector-treated mice. HER2dMAb sera effectively killed the ovarian cancer cells in the presence of PBMCs, similar to commercially available Hu4D5, but not in their absence. No killing was observed in the control sera conditions (Figure 3B and Supplemental Figure 1B) or against HER2-cell lines, such as MDA-MB-231 (Supplemental Figure 1C). Similarly, HER2dMAb showed antibody-dependent phagocytosis activity (Supplemental Figure 1D).. HER2dMAb delays cancer progression in vivo. To determine the antitumor effects of HER2dMAb in vivo, we challenged nude mice with the OVCAR3 ovarian cancer cell line. Nude mice have no T cells but present enhanced NK and macrophage activity (13), and their splenocytes can lyse OVCAR3 ...
Small-cell lung cancer (SCLC) accounts for 15% of all lung cancer cases and is a highly lethal disease. For the last several decades, the standard treatment for SCLC has been deadlocked, and new therapeutic strategies are urgently needed. Human epidermal growth factor receptor 2 (HER2) is a member of the HER family and has been reported to be overexpressed in 30% of SCLC cases with poor prognosis. However, the clinical relevance of HER2-targeted therapy for SCLC remains unclear. Here, we firstly identify that cytotoxic drugs induce significant HER2 overexpression through microRNA-125a (miR-125a) and miR-125b downregulation, which in turn act as a novel therapeutic target for trastuzumab-mediated cellular cytotoxicity in SCLC. In this study, we showed that treatment of the HER2-positive SCLC cells, SBC-3 and SBC-5, with cytotoxic drugs induced a significant upregulation of HER2. Cisplatin (CDDP) treatment of SCLC cells resulted in a significant downregulation of miR-125a and miR-125b. We ...
An immune-based approach to allow antibodies in the plasma of HIV-1-infected individuals to regain their activity of antibody-dependent complement-mediated lysis (2010 ...
Jurkat-Lucia™ NFAT-CD16 cells are human reporter cells for the early nuclear translocation of NFAT upon antibody-dependent cellular cytotoxicity (ADCC) induction. A bioluminescent signal is produced by an NFAT-dependent Lucia luciferase reporter protein.
Rituximab (RTX), an anti-CD20 antibody, revolutionized treatment for B-cell malignancies, but it is not without its own shortcomings, most notably tumor relapse. Recent research has provided evidence supporting the increased efficacy of RTX when combined with interleukin-15 (IL-15). IL-15 enhances antibody-dependent cellular cytotoxicity (ADCC), an important mechanism of RTX, by increasing the proliferation and activation of natural killer (NK) cells, as well as monocytes and macrophages. However, the majority of this evidence has been obtained through in vitro experiments and in vivo models using xenografts in immuno-deficient mice. Given the complexity of the immune system, we used an immuno-competent, syngeneic mouse model of human B-cell lymphoma to further investigate the effect of combining IL-15 with RTX to enhance ADCC. Wild-type (WT) C57BL/6 mice (n = 40) were distributed into treatment groups of 10 mice each, and inoculated intravenously with EL4-CD20 cells, a mouse lymphoma line ...
The clinical introduction of rituximab has dramatically changed the treatment strategy for follicular lymphoma. The improvement in time to progression with rituximab-combined chemotherapy has been reported (14). Relapsed cases are often resistant to doxorubicin; therefore, when the total dose of doxorubicin is taken into consideration, the development of cardiotoxicity by salvage therapy is worrisome. Recently, several studies reported that the cytotoxic effect of rituximab is increased by combination with various cytokines (15-17). It has been suggested that the treatment effect of rituximab is increased by combination with G-CSF because G-CSF increases the cytotoxicity of neutrophils through ADCC (18). We previously reported that when the R-CHOP regimen was combined with G-CSF, G-CSF increased FcγR1 (CD64) expression on neutrophils and ADCC activity. Because there were no significant differences in the degree of increase of CD64 expression and ADCC activity between those who had been treated ...
While antiretroviral therapy (ART) can completely suppress viremia, it is not a cure for HIV. HIV persists as a latent reservoir of infected cells, able to evade host immunity and re-seed infection following cessation of ART. Two promising immunotherapeutic strategies to eliminate both productively infected cells and reactivated cells of the reservoir are the adoptive transfer of potent HIV-specific T cells and the passive administration of HIV-specific broadly neutralizing antibodies also capable of mediating antibody-dependent cellular cytotoxicity (ADCC). The simultaneous use of both as the basis of a single therapeutic has never been explored. We therefore sought to modify HIV-specific T cells from HIV-naive donors (to allow their use in the context of allotransplant, a promising platform for sterilizing cures) so they are able to secrete a broadly neutralizing antibody (bNAb) directed against the HIV envelope to elicit ADCC. We designed an antibody construct comprising bNAb 10-1074 heavy and light
The open CD4-bound conformation of HIV-1 envelope glycoproteins is the primary target of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies present in HIV-positive (HIV+) sera, such as anti-coreceptor binding site and anti-cluster A antibodies. Here we report that the binding of these two families of antibodies is required to engage FcγRIIIa and mediate ADCC. ...
Leukocyte integrins are intimately involved in transient adherence of leukocytes to endothelium and to each other in the processes of extravasation and cell activation. In this study, seven mAb directed against human CD11a and two mAb directed against human CD18, the alpha- and beta-chains of the leukocyte functional Ag-1 molecule, respectively, were analyzed for their ability to inhibit several leukocyte functional Ag-1-mediated interactions. The best blocking mAb in these studies, a rat anti-human CD18, YFC51.1, was subsequently humanized by complementarily-determining region grafting, associated with human C regions and expressed. The humanized mAb was shown to maintain binding for human CD18. Even though the humanized mAb was an IgG1 isotype it still retained the functional blocking characteristics of the rat mAb while failing to mediate cell killing. The IgG1 mAb was unable to bind human Clq and could block but did not mediate antibody-dependent cellular cytotoxicity.
The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format. By default, clicking on the export buttons will result in a download of the allowed maximum amount of items. To select a subset of the search results, click Selective Export button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export. After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format. ...
Ting, C; Nunn, N E.; Park, J Y.; and Herberman, R B., Comparison of three isotopic assays of cell-mediated cytotoxicity against mouse tumor cells. II. Sensitivity and specificity of the assays and characteristics of effector and sensitizing cells. (1977). Subject Strain Bibliography 1977. 1932 ...
Antibody-dependent cellular cytotoxicity (ADCC) has recently been identified as one of the critical mechanisms underlying the clinical efficacy of therapeutic antibodies, especially anticancer antibodies. Therapeutic antibodies fully lacking the core fucose of the Fc oligosaccharides have been found to exhibit much higher ADCC in humans than their fucosylated counterparts. However, data which show how fully non-fucosylated antibodies achieve such a high ADCC in human whole blood have not yet been disclosed. The precise mechanisms responsible for the high ADCC mediated by fully non-fucosylated therapeutic antibodies, even in the presence of human plasma, should be explained based on direct evidence of non-fucosylated antibody action in human blood. Using a human ex vivo B-cell depletion assay with non-fucosylated and fucosylated anti-CD20 IgG1s rituximab, we monitored the binding of the therapeutic agents both to antigens on target cells (target side interaction) and to leukocyte receptors (FcγR) on
BioAssay record AID 102327 submitted by ChEMBL: Cytotoxicity activity on LoVo/Dx human adenocarcinoma cell line after 1 hr of drug exposure.
The phenomenon of antibody-mediated target Cell destruction by non-sensitized effector Cells. The identity of the target Cell varies, but it must possess surface Immunoglobulin G whose Fc portion is intact. The effector Cell is a killer Cell possessing Fc Receptors. It may be a Lymphocyte lacking conventional B- or T-Cell markers, or a Monocyte, Macrophage, or polynuclear Leukocyte, depending on the identity of the target Cell. The reaction is Complement-independent ...
The phenomenon of antibody-mediated target Cell destruction by non-sensitized effector Cells. The identity of the target Cell varies, but it must possess surface Immunoglobulin G whose Fc portion is intact. The effector Cell is a killer Cell possessing Fc Receptors. It may be a Lymphocyte lacking conventional B- or T-Cell markers, or a Monocyte, Macrophage, or polynuclear Leukocyte, depending on the identity of the target Cell. The reaction is Complement-independent ...
Franco, P; Veronese, F; Levi, F; Goldin, A; and Nicolin, A, Antibody-dependent cellular cytotoxicity against drug-induced antigens in l5178y mouse lymphoma. (1982). Subject Strain Bibliography 1982. 3308 ...
The primary goal of this study was to determine whether the known antibody-dependent cytotoxicity of Edrecolomab (18) could be monitored in advanced breast cancer patients by repeating immunocytochemical bone marrow aspiration before and after antibody infusion. We were able to demonstrate that typing for EpCAM expression of micrometastatic breast cancer cells defined these cells as suitable targets of Edrecolomab, which was originally thought to be a cytotoxic agent for colorectal cancer cells only. Because extrapolation from antigen patterns expressed by the primary tumor has been shown to be unreliable (23) , phenotyping of bone marrow micrometastases by double-labeling techniques thus may help enlarge the therapeutic spectrum of monoclonal antibody therapy. On the basis of our present data, we believe that antigen expression by micrometastatic cells may be a better predictor of response to antibody-based therapy than expression by the related primary tumor. Our pilot study provides data that ...
The epidermal growth factor receptor (EGFR) is a widely expressed Ag that is successfully targeted in tumor patients by mAbs or tyrosine kinase inhibitors. A clinical study in non-small cell lung cancer patients demonstrated a positive correlation between EGFR expression levels and the therapeutic efficacy of the EGFR mAb cetuximab. However, the impact of EGFR expression on the different mechanisms of action (MoAs) triggered by the EGFR mAb has not been defined. In this study, BHK-21 cells were stably transfected to express different EGFR levels, which were quantified by immunofluorescence and immunohistochemistry and compared with EGFR levels of clinical non-small cell lung cancer samples. These cells were used to systematically investigate the impact of target Ag expression levels on Fab- or Fc-mediated MoAs of EGFR mAb. A negative correlation between EGFR levels and potency of Fab-mediated MoA was observed. Interestingly, Ab-dependent cell-mediated cytotoxicity (ADCC) by NK cells, monocytes, ...
Introduction: Elotuzumab, a humanized IgG1 monoclonal antibody that binds to SLAMF7 expressed on myeloma and natural killer (NK) cells, has a dual mode of action; it causes targeted myeloma cell death by directly activating NK cells and enhances NK cell-mediated antibody-dependent cellular cytotoxicity. Elotuzumab combined with lenalidomide and dexamethasone (ELd) has been approved in Japan for the treatment of relapsed/refractory multiple myeloma (RRMM). In a 4-y follow-up of the phase 3 ELOQUENT-2 study (NCT01239797) in patients (pts) with RRMM, ELd demonstrated a sustained 29% reduction in risk of disease progression/death and an overall survival benefit vs Ld (Dimopoulos M et al. Haematologica 2017), consistent with prior reports (Dimopoulos M et al. Br J Haematol 2017). We present the first report on the efficacy/safety of ELd vs Ld in pts with newly diagnosed multiple myeloma (NDMM). Methods: In this phase 2, open-label, multicenter study (NCT02272803) in Japan enrolling pts with NDMM ...
HIV-1-contaminated cells giving a video presentation envelope glycoproteins (Env) in the Compact disc4-certain conformation about their surface area are preferentially targeted by antibody-dependent cellular-mediated cytotoxicity (ADCC). we check out the impact of the Phe 43 cavity on ADCC reactions. Filling up this cavity with a histidine or tryptophan remains in Env with a organic serine remains at this placement (T375H/Watts) improved the susceptibility MP470 of HIV-1-contaminated cells to ADCC. On the other hand, the alternative of His 375 by a serine residue (L375S) within HIV-1 CRF01_AE reduced the effectiveness of the ADCC response. Our outcomes increase the interesting probability that the existence of His 375 in the moving stress where the Mobile home144 trial was kept led to the noticed vaccine effectiveness. IMPORTANCE HIV-1-contaminated cells offering Env in the Compact disc4-destined conformation on their surface area are preferentially targeted by ADCC mediated by HIV-positive ...
Endogenous plasma IgG sets an immunological threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP). Here we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors ...
The characterization of protective Ab responses to influenza virus in mouse models has typically focused on Nab function. However, recent studies suggest that the nonneutralizing functions provided by the Fc region of the Ab are important for the potency and the protective ability of HA-specific Abs (22, 51). A study by Corti et al. (22) showed that the broadly neutralizing human FI6 Ab attributes most of its in vivo activity to its FcR-binding properties. Mice administered 3 mg/kg of the FcR mutant (termed FI6-LALA) FI6 Ab had a 60% reduction in survival compared with FI6 Ab or FI6 complement mutant (termed FI6-KA) when challenged with a lethal dose of PR8 virus. However, the transfer of human IgG1 Abs into mice that express mouse FcR may be suboptimal. A recent study by DiLillo et al. (52) showed that administration of 4 mg/ml of a mouse IgG2a form of FI6 Ab (which can mediate ADCC in mice) protected mice from lethal challenge, whereas 4 mg/ml of mouse IgG1 FI6 Ab form (which does not mediate ...
Read this chapter of Tabers® Cyclopedic Medical Dictionary, 23e online now, exclusively on F.A. Davis PT Collection. F.A. Davis PT Collection is a subscription-based resource from McGraw Hill that features trusted content from the best minds in PT.
These are all influencing factors of the interaction between the mAb and the antigen (or mAb and effector molecules) and thus should be evaluated at an early stage of biosimilar development prior to final lead molecule identification.. In particular, the carbohydrate profile is important for the evaluation of complex effector functions, including Antibody-dependent Cell-mediated Cytotoxicity (ADCC) and Complement-dependent cytotoxicity (CDC).. The glycosylation profile of a mAb can vary in terms of:. ...
Campath-1H is a humanized monoclonal antibody targeted against the CDw52 membrane antigen of lymphocytes, which causes complement and antibody-dependent cell-mediated cytotoxicity. Campath-1H has...
Natural killer (NK) cells are important lymphocytes with potent anti-tumor and anti-viral functions. In recent years there has been a significant increase in knowledge about the mechanisms regulating NK-cell functions. Furthermore, NK cells play an important role in preventing relapse in patients with myeloid malignancies after allogeneic hematopoietic cell transplantation.1,2 Also, due to their anti-leukemia properties, there has been a keen interest in the use of NK cells in novel adoptive transfer protocols for patients with hematologic and non-hematologic malignancies.3-5. Human NK cells are negative for CD3 expression but uniformly express CD56, and based on CD56 and CD16 expression, two main subsets are present in the peripheral blood: CD56highCD16low/− and CD56lowCD16high. CD16 is the low affinity IgG receptor (FcγRIII) and human NK cells exclusively express CD16a, a transmembrane protein critical for mediating antibody dependent cell cytotoxicity (ADCC) function of NK cells. CD16 is ...
In preclinical studies, MOR202 mediated antibody-dependent cell-mediated cytotoxicity in MM cells derived from patients in vitro. Either Velcade® (bortezomib) or Revlimid® (lenalidomide) enhanced the cytotoxic activity of MOR202 in vitro and also the inhibition of MM-mediated bone lysis and tumor load in vivo. The enhancement by bortezomib was mediated through a direct cytotoxic effect on MM cells.. Lenalidomide synergistically enhanced MOR202 activity by several mechanisms identified to be direct cytotoxicity, activation of effector cells and increased CD38 expression levels on MM cells. In an orthotopic xenograft murine model of multiple myeloma, MOR202 reduced tumor load and tumor mediated bone lysis. Co-administration of MOR202 with either bortezomib or lenalidomide completely abolished bone lysis in a synergistic manner. These findings support further investigation of MOR202 combination regimens in clinical trials. MOR202 is currently being tested in a phase 1/2a trial in patients with ...
In preclinical studies, MOR202 mediated antibody-dependent cell-mediated cytotoxicity in MM cells derived from patients in vitro. Either Velcade® (bortezomib) or Revlimid® (lenalidomide) enhanced the cytotoxic activity of MOR202 in vitro and also the inhibition of MM-mediated bone lysis and tumor load in vivo. The enhancement by bortezomib was mediated through a direct cytotoxic effect on MM cells.. Lenalidomide synergistically enhanced MOR202 activity by several mechanisms identified to be direct cytotoxicity, activation of effector cells and increased CD38 expression levels on MM cells. In an orthotopic xenograft murine model of multiple myeloma, MOR202 reduced tumor load and tumor mediated bone lysis. Co-administration of MOR202 with either bortezomib or lenalidomide completely abolished bone lysis in a synergistic manner. These findings support further investigation of MOR202 combination regimens in clinical trials. MOR202 is currently being tested in a phase 1/2a trial in patients with ...
BSB 753A-B. Research Interests. The primary focus of my laboratory is directed towards understanding the mechanisms underlying the involvement of immunoglobulin Fc (GM) and Fcgamma receptor genes in immunity to various malignant and infectious diseases. These studies are supported in part by grants and contracts from the National Institutes of Health and the Department of Defense.. Recent Publications , Additional Publications. Pandey JP, Namboodiri AM. (2014) Genetic variants of IgG1 antibodies and FcgRIIIa receptors influence the magnitude of antibody-dependent cell-mediated cytotoxicity against prostate cancer cells. OncoImmunology 3:e27317.. Pandey JP, Kistner-Griffin E, Black L, Namboodiri AM, Iwasaki M, Kasuga Y, Hamada GS, Tsugane S. (2014) IGKC and FcgR genotypes and humoral immunity to HER2 in breast cancer. Immunobiology 219:113-117.. Pandey JP. (2014) Genetic etiology of schizophrenia: possible role of immunoglobulin g genes. Psychiatr Genet 24:83-86.. Pandey JP, Namboodiri AM, Ohue ...
Japans largest platform for academic e-journals: J-STAGE is a full text database for reviewed academic papers published by Japanese societies
Promega Corporation has announced the introduction of a novel bioluminescent assay for the quantification of Fc effector function of antibody-based molecules in the development and manufacture of biologic drugs. The assay is ADCC mechanism of action (MOA)-based and features frozen, thaw-and-use effector cells, and optimized reagents and protocol to perform a reporter-based ADCC bioassay in a single day. The ADCC Reporter Bioassay correlates with classic cytotoxic ADCC assays and is a sui
Persons who have been VACCINATED against COVID-19 are now subject to Antibody-Dependent Enhancement which is highly likely to . . . kill them. This is the absolute worst-case scenario with any vaccine. People who took the vax should be quarantined and isolated immediately. The
CD16 is a 50-80 kDa glycoprotein that is expressed in two different isoforms. The transmembrane form is found on human NK cells, macrophages, and mast cells, while the glycosylphosphatidylinositol (GPI)-linked form is present on neutrophils. The human CD16 antigen is a low-affinity receptor for aggregated IgG. The transmembrane form plays a role in signal transduction, NK cell activation, and antibody-dependent cellular cytotoxicity. Clone VEP13 recognizes both the extracellular domain of the transmembrane form as well as the GPI-linked form of the human CD16 antigen. CD16 is expressed on the majority of rhesus monkey NK cells and on a subset of monocytes but not on granulocytes. - Österreich
Struchium sparganophora (Linn) Ktze, (Asteraceae) is a culinary herbs used as part of a traditional dish in Nigeria and a medicinal plants for the treatment of different ailments in Africa. Dried leaf, stem and root parts of this plant were extracted with n-hexane, chloroform and methanol respectively, concentrated under reduced pressure, freeze dried and evaluated for their antimicrobial and anti tumour activities. The antimicrobial test involved microdilution titre technique while cytotoxicity activities was evaluated using the 3,-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. The extracts exhibited a broad spectrum of activity against Gram- positive and Gram-negative organism of minimum inhibitory concentration (MIC) of 50 to 6.25 mg/ml but this activity is less than that of anti-microbial standard drug amoxicillin which had MIC of 0.78 to 6.25 mg/ml except against Klebsiella aerogenes on which the extracts had a similar activity to that amoxicillin of MIC 6.25 ...
Rituximab is a therapy no used in both indolent and aggressive B cell lymphomas. What is the mechanism of action of Rituximab? List the major disorders for which Rituximab is approved for use.. Recall that CD20 is expressed on over 90% of B cells and is a protein that is not shed or internalized.. Rituximab is an anti-CD20 chimeric monoclonal antibody that on contact to CD20 on the surface of a B cell causes cytotoxicity mediated by compliment and antibody-dependent cellular cytotoxicity.. Indications for Rituximab use:. ...
Radiation therapy (RT) and immunotherapy of cancer both date back more than 100 years, and yet, because radiation was often considered immunosuppressive, there had been little enthusiasm for combining them until recently. Immunotherapy has an established role in the treatment of some cancers-superficial bladder cancer treated with bacillus Calmette-Guérin (BCG), renal cell carcinoma and melanoma treated with interferon and interluekin (IL)-2 (Proleukin), and breast cancer and lymphoma treated with monoclonal antibodies such as trastuzumab (Herceptin) and rituximab (Rituxan), which partly function through antibody-dependent cellular cytotoxicity.
We investigated a fixed scheme of combination chemotherapy protocol including CHOP, granulocyte colony stimulating factor (G-CSF) and rituximab (CHOP-GR) for patients with advanced-stage grade 1 or grade 2 follicular lymphoma in a phase II clinical trial, assessing enhancement of antibody-dependent cellular cytotoxicity of rituximab by G-CSF ...
RV144 remains the only HIV-1 vaccine trial to demonstrate efficacy against HIV-1 acquisition. The prespecified analysis of immune correlates of risk showed that antibodies directed against the V1V2 region of gp120, in particular the IgG1 and IgG3 subclass mediating antibody-dependent cell-mediated c …
Many broadly reactive human being monoclonal antibodies against the hemagglutinin (HA) stem of influenza A trojan have been established for therapeutic applications. inhibiting trojan particle discharge. These findings broaden our understanding of the systems where broadly reactive stem-targeting antibodies inhibit viral replication and offer valuable details for general vaccine development. by interfering with viral membrane fusion during viral entrance predominantly. A number of the anti-HA stem antibodies need Fc receptor-mediated antibody-dependent mobile cytotoxicity (ADCC) to cover efficient protection to lessen the amount of contaminated cells (DiLillo et al., 2014, DiLillo et al., 2016, Jegaskanda et al., 2014). Hence, many antibody-dependent inhibitory systems serve to safeguard against influenza A trojan infection Protective Efficiency from the mAbs in Mice Baseline body weights of 6-week-old feminine BALB/c mice (Japan SLC) had been assessed. Four mice (arbitrarily chosen) per group ...
ProBioGen has announced the launch of a comprehensive set of engineered, royalty-free biopharmaceutical CHO production cell lines, individually optimized for enhanced ADCC activity, adjusted galactosylation levels and/or increased production of the target antibodies or proteins. This elaborate cellular toolbox allows the rapid and targeted creation of antibody and protein molecules with specific pre-defined properties.
Antibody testing standards are well underway. But validation relies on numerous orthogonal methods, and for best results, a combination of antibody-dependent and antibody-independent testing methods is suggested.
To protect your privacy, your account will be locked after 6 failed attempts. After that, you will need to contact Customer Service to unlock your account.. You have 4 remaining attempts.. You have 3 remaining attempts.. You have 2 remaining attempts.. You have 1 remaining attempt.. Contact Customer Service ...
اطلاعات مندرج در این پایگاه فقط جهت مطالعه کاربران با رعایت شرایط اعلام شده است. نسخه‌برداری و بازنشر اطلاعات به هر روش، در هر نوع رسانه و با هر هدفی ممنوع و پیگرد قانونی دارد. ...
Antibody-dependent cell-mediated cytotoxicity (ADCC) requires antibodies to bind to target cell surfaces. Antibodies are formed ... known as complement-dependent cytotoxicity; enhancement of antibody-dependent cell-mediated cytotoxicity; and CR3-dependent ... Fc receptors are found on many immune system cells, including NK cells. When NK cells encounter antibody-coated cells, the ... "Natural killer cell mediated antibody-dependent cellular cytotoxicity in tumor immunotherapy with therapeutic antibodies". ...
It triggers antibody-dependent cell-mediated cytotoxicity (ADCC). It does this by activating natural killer cells by binding to ... CAIX is expressed on the surface of most renal cancer cells and is hypothesized to be on the surface of other tumor cells. It ... Its development was suspended as a "naked" or unconjugated antibody during phase III trials due to efficacy. Girentuximab was ... Bedke J, Stenzl A (2013). "Immunotherapeutic strategies for the treatment of renal cell carcinoma: where are we now?". Expert ...
Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell- ... Lirentelimab depletes eosinophils via antibody-dependent natural killer cell mediated cytotoxicity. Lirentelimab is a humanized ... August 2020). "An anti-siglec-8 antibody depletes sputum eosinophils from asthmatic subjects and inhibits lung mast cells". ... Lirentelimab inhibits mast cells' IgE-mediated degranulation and de novo synthesis of prostaglandin D2 in vitro. Mild-to- ...
This is thought to enhance its antibody-dependent cell-mediated cytotoxicity. It was first tested in humans in 2007. Kyowa ... Kyowa humanized it, and expressed the humanized gene in a CHO cell line in which FUT8 had been knocked out, which produced ... It was approved in Japan in 2012, for the treatment of relapsed or refractory CCR4+ adult T-cell leukemia/lymphoma (ATCLL) and ... Yu X, Marshall MJ, Cragg MS, Crispin M (June 2017). "Improving Antibody-Based Cancer Therapeutics Through Glycan Engineering" ( ...
Meanwhile, antibody-dependent cell cytotoxicity (ADCC) remains unchanged in XLPDR NK cells. The most common manifestations of ... discovered that POLA1 deficiency is associated with decreased direct cytotoxicity of NK cells due to disturbances in vesicular ... and impaired direct cytotoxicity of NK cells are the most common symptoms. In females the disease is characterized by skin ... November 2019). "NK cell defects in X-linked pigmentary reticulate disorder". JCI Insight. 4 (21). doi:10.1172/jci.insight. ...
They cause thyroid cell damage by complement activation and antibody dependent cell cytotoxicity. However, anti-TPO antibodies ... The production of antibodies in Graves' disease is thought to arise by activation of CD4+ T-cells, followed by B-cell ... These B-cells produce antibodies specific to the thyroid antigens. In Hashimoto's thyroiditis, activated CD4+ T-cells produce ... of anti-TPO antibody positive cases also demonstrate thyroglobulin antibodies. Anti-Na+/I− symporter antibodies are a more ...
Antibody-dependent cell-mediated cytotoxicity: detection by automated flow cytometry with ultramicro techniques. Science. 1980 ... Prognostic and predictive value of a malignancy-risk gene signature in early-stage non-small cell lung cancer. Journal of the ... Increased Src activity disrupts cadherin/catenin-mediated homotypic adhesion in human colon cancer and transformed rodent cells ...
... or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as ... This process is known as antibody-dependent cell-mediated cytotoxicity (ADCC). FcγRIII on NK cells can also associate with ... Another process involving Fc receptors is called antibody-dependent cell-mediated cytotoxicity (ADCC). During ADCC, FcγRIII ... CD4+ T cells (mature Th cells) provide help to B cells that produce antibodies. Several subsets of activated effector CD4+ T ...
... s are also capable of killing infected host cells via antibody-dependent cell-mediated cytotoxicity. Vacuolization may ... "Nr4a1-Dependent Ly6Clow Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal". Cell. 153 (2): 362-375. doi: ... cell surface marker was shown to give an unequivocal separation of the two cell types. Ghattas et al. state that the " ... bipotent cells that differentiated from hematopoietic stem cells. Monocytes circulate in the bloodstream for about one to three ...
... complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and antibody-dependent phagocytosis. These ... Ansuvimab has been found to be capable of killing cells by antibody-dependent cell-mediated cytotoxicity. Other functional ... Antibodies are also able to "kill" virus particles directly and/or kill infected cells using antibody-mediated "effector ... The drug is composed of a single monoclonal antibody (mAb) and was initially isolated from immortalized B-cells that were ...
... cells. When expressed, CD32C plays an important role in the activation of antibody-dependent cell cytotoxicity (ADCC). Animal ... The therapeutic usage of monoclonal antibodies against CD32B can be effective for inducing cytotoxicity against B cell lymphoma ... Having too little CD32B has been associated with dysregulated antibody function, as well as increased antibody-dependent ... CD32 can be found on the surface of a variety of immune cells. CD32 has a low-affinity for the Fc region of IgG antibodies in ...
October 2019). "Imlifidase Inhibits HLA Antibody-Mediated NK Cell Activation and Antibody-Dependent Cell-Mediated Cytotoxicity ... including CDC and antibody-dependent cell-mediated cytotoxicity (ADCC). Thus, imlifidase reduces the level of donor specific ... It cleaves the heavy chains of all human IgG subclasses (but no other immunoglobulins), eliminating Fc-dependent effector ... November 2018). "Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS ( ...
This choice was made as TGN1112 showed antibody-dependent cellular cytotoxicity on CD28+ Jurkat cells. Thus the function of ... However, cell opsonisation by antibody leads normally to phagocytosis of the labeled cells, as seen in the case of HIV. The ... Thus, attempts to induce FOXP3+ T cells might also induce effector cells capable of causing tissue damage. Other cells ... Since CD28 is the target of the TGN1412 antibody, M. fascicularis effector T-cells could not be stimulated by the drug. In 2013 ...
Nevertheless, antibody-dependent, cell-mediated cytotoxicity is a substantial factor behind the apoptotic fall-out of ... Iodine also promotes follicular cell apoptosis and has an influence on immune cells (augmented maturation of dendritic cells, ... IFN-γ promotes cell-mediated cytotoxicity against thyroid. Mutations causing increased production of IFN-γ were associated with ... Weaker T-cell signaling may lead to impaired thymic deletion of autoreactive T cells, and increased PTPN22 function may result ...
It is an unconjugated antibody, thought to work via the activation of antibody-dependent cell-mediated cytotoxicity (ADCC). It ... October 1983). "Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human ... It is a monoclonal antibody that binds to CD52, a protein present on the surface of mature lymphocytes, but not on the stem ... Alemtuzumab is used for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in people who have been treated with ...
... a polarization of B cells that augments its therapeutic function in NK-cell-mediated antibody-dependent cellular cytotoxicity ... The Fc portion of rituximab mediates antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC ... The antibody binds to the cell surface protein CD20. CD20 is widely expressed on B cells, from early pre-B cells to later in ... antibody-dependent cellular cytotoxicity). This strategy for enhancing a monoclonal antibody's ability to induce ADCC takes ...
... binds to BCMA on myeloma cell surfaces causing cell cycle arrest and inducing antibody-dependent cellular cytotoxicity. ... Belantamab mafodotin is a humanized IgG1κ monoclonal antibody against the B-cell maturation antigen (BCMA) conjugated with a ... March 2019). "Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy ... of Two Doses of GSK2857916 in Participants With Multiple Myeloma Who Have Failed Prior Treatment With an Anti-CD38 Antibody" at ...
... the antibody itself may trigger cell death via antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent ... The antibody binds to the CD20 antigen found on the surface of normal and malignant B cells (but not B cell precursors), ... Together, these actions eliminate B cells from the body, allowing a new population of healthy B cells to develop from lymphoid ... Compared to other monoclonal antibody treatments (many of which are well over US$40,000 for a course of therapy), it may be ...
These receptors bind to the Fc portion of IgG antibodies, which then activates antibody-dependent cell-mediated cytotoxicity ( ... involved in antibody-dependent cellular cytotoxicity (ADCC). It can be used to isolate populations of specific immune cells ... by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) in NK cells. However, this pathway can also be ... zeta complex in human natural killer cells. Induction by antibody-dependent cytotoxicity but not by natural killing". Journal ...
... the efficacy of these antibodies in vivo is believed to be a result of antibody-dependent cell-mediated cytotoxicity and the ... "Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses". Cell. 166 (3): 609-623. doi:10.1016/j.cell ... Therefore, HA is responsible for binding Influenza virus to sialic acid on the surface of target cells, such as cells in the ... Firstly, it allows the recognition of target vertebrate cells, accomplished through the binding to these cells' sialic acid- ...
... causing cells to apoptose via antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, inhibition of ... Antibody-dependent cellular cytotoxicity is by means of natural killer cells. Unlike isatuximab which causes apoptosis directly ... Multiple myeloma cells with higher levels of CD38 show greater daratumumab-mediated cell lysis than cells with low CD38 ... which tends to mask the presence of any clinically significant antibodies. Treatment of the antibody panel cells with ...
... or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as ... NK cells. Macrophages (certain tissues) Induction of antibody-dependent cell-mediated cytotoxicity (ADCC). Induction of ... This process is known as antibody-dependent cell-mediated cytotoxicity (ADCC). FcγRIII on NK cells can also associate with ... CD4+ T cells provide help to B cells that produce antibodies. Several subsets of activated effector CD4+ T cells are observed ...
... suggest a response of CR3 and CR4 to enable complement-dependent cell cytotoxicity towards antibody-coated cancer cells. Such ... they are involved in enhancing complement-dependent cytotoxicity in NK cells. Immunomodulatory therapies often aim for an ... phagocytosis and other cell-cell interactions in a variety of cells and circumstances. Upregulation of Mac-1 in the presence of ... Different faces of CR3 and CR4 in myeloid and lymphoid cells of mice and men" (PDF). Seminars in Cell & Developmental Biology. ...
The results of antibody-dependent cellular cytotoxicity assay on guineas-pig Kurloff cells strongly indicate an immunological ... Also, Kurloff cells present antibody-dependent cytotoxic activity in vitro. The structure of Kurloff cell was identified using ... "Antibody-dependent cellular cytotoxicity in the guinea pig: the role of the Kurloff cell". Cellular Immunology. 55 (2): 312-27 ... Antibody-Dependent Cellular Cytotoxicity (ADCC)", Antibody Fc, Academic Press, pp. 1-27, ISBN 978-0-12-394802-1, retrieved 2020 ...
The contribution of antibody-dependent cell-mediated cytotoxicity to tumor cell killing can be measured with a specific test ... NK cells are thought to be an important cell type in this process. These cells are known as "uterine NK cells" (uNK cells) and ... plays a role in antibody-dependent cell-mediated cytotoxicity; in particular, they bind Immunoglobulin G. Killer-cell ... CD56dim NK cells are always CD16 positive (CD16 is the key mediator of antibody-dependent cellular cytotoxicity (ADCC). ...
... targets tumor cells and causes apoptosis through the immune system by promoting antibody-dependent cellular cytotoxicity. Two ... Cell. 125 (6): 1137-1149. doi:10.1016/j.cell.2006.05.013. ISSN 0092-8674. PMID 16777603. S2CID 14256004. Garrett TP, McKern NM ... Lack of Schwann cell maturation leads to degeneration of motor and sensory neurons. Excessive ErbB signaling is associated with ... Cell. 11 (2): 507-517. doi:10.1016/S1097-2765(03)00047-9. PMID 12620237. Franklin MC, Carey KD, et al. (2004). "Insights into ...
Antibody dependent cell mediated cytotoxicity). It was shown that in order to initiate ADCC in vitro, PMN's have to adhere to ... On T cells and B cells, trogocytosis is triggered when the T cell receptor (TCR) on T cells or B cell receptor (BCR) on B cells ... from the cells they scan. The transfer was cell contact-dependent and occurred in the context of cell-conjugate formation. ... affinity T cell down-modulation of costimulatory molecules on dendritic cells mediated by T cells leads to regulation of T cell ...
... and the induction of antibody-dependent cellular cytotoxicity of virus-infected cells. Bavituximab inhibited replication of ... which is a component of cell membranes that is exposed when a cell is transformed into solid tumor cancer cell or dies, and ... As of January 2016, bavituximab had been in a Phase III clinical trial for non-small cell lung cancer (NSCLC), a Phase II/III ... Bavituximab is an antibody that binds to complexes of the phosphatidylserine-binding plasma protein β2-glycoprotein 1 and ...
Indeed, the engagement of CD16a on CD3+CD56+ cells led to a potent antibody-dependent cell-mediated cytotoxicity (ADCC) both in ... CIK cells have, as a key feature, a double T-cell and NK cell-like phenotype. This unique combination of T-cell and NK-cell ... CIK cells is distinctive from that of natural killer cells or LAK cells because they can lyse cells that NK cells and LAK cells ... Besides recognition via TCR/CD3, NK-cell-like tumor recognition is mediated by cell-cell contact-dependent NKG2D, DNAM-1 and ...
... of natural killer cells by antibodies initiates a cytotoxic mechanism known as antibody-dependent cell-mediated cytotoxicity ( ... Activated B cells differentiate into either antibody-producing cells called plasma cells that secrete soluble antibody or ... The "knobs-into-holes" shape facilitates antibody dependent cell mediated cytotoxicity. Single chain variable fragments (scFv) ... The antibody isotype of a B cell changes during cell development and activation. Immature B cells, which have never been ...
... make it useful for making cell lines that can be used to test serotyping antibodies. As a result, HLA-A1 and B8 produce some of ... In insulin dependent diabetes mellitus[edit]. In type 1 diabetes both DR3 and DQ2 appear to play a role. DR3-DQ2.5 can be ... whereas class I mediated cytotoxicity is not. MICA and MICB are intestinally expressed. There are many genes that lie on either ... of these half had anti-transglutaminase antibodies, but few had endomysial antibody.[29] This could indicate an association ...
The cytotoxicity of Natural Killer (NK) cells and the antigen-presenting function of dendritic cells is known to diminish with ... which are specialized in facilitating peripheral B cell maturation, and the generation of antibody-producing plasma cells and ... Once matured and circulating throughout the peripheral system, T-cells still undergo deleterious age-dependent changes. ... Mocchegiani, E; M. Malavolta (2004). "NK and NKT cell functions in immunosenescence". Aging Cell. 3 (4): 177-184. doi:10.1111/j ...
... antibodies - antibody-dependent cell-mediated cytotoxicity (ADCC) - antibody-mediated immunity - antifungal medication - ... T suppressor cells - T4 cell - T4 cells (T-helper cells) - T8 cells - Tanner staging - TAT - TB - template - TeachAIDS - ... B-cell lymphoma - B cells - B lymphocytes (B cells) - bactericidal - bacteriostatic - bacterium - baculovirus - baseline - ... cells - CDC National Prevention Information Network (CDC-NPIN) - cell lines - cell-mediated immunity (CMI) - cellular immunity ...
2007). "TNF Trafficking to Human Mast Cell Granules: Mature Chain-Dependent Endocytosis". The Journal of Immunology. 178 (9): ... This inhibition can be achieved with a monoclonal antibody such as infliximab (Remicade) binding directly to TNFα, adalimumab ( ... "Lymphocyte in vitro cytotoxicity: characterization of human lymphotoxin". Proc. Natl. Acad. Sci. U.S.A. 61 (4): 1250-5. ... positive regulation of heterotypic cell-cell adhesion. • negative regulation of mitotic cell cycle. • endothelial cell ...
cell cycle arrest. • learning or memory. • cellular copper ion homeostasis. • cellular response to copper ion. • cell cycle. • ... ATP-dependent protein binding. • metal ion binding. • tubulin binding. • protein binding. • identical protein binding. • copper ... Modulation of signal transduction pathways has been demonstrated in cross-linking with antibodies and ligand-binding (hop/STI1 ... some studies mitigate claims for a direct link between PrPSc and cytotoxicity.[25] ...
... (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a ... "Antibody-dependent cell-mediated cytotoxicity against influenza virus-infected cells". The Journal of Infectious Diseases. 148 ... Antibody-Dependent+Cell+Cytotoxicity at the US National Library of Medicine Medical Subject Headings (MeSH) ... By NK cells[edit]. The typical ADCC involves activation of NK cells by antibodies. An NK cell expresses Fc receptors, mostly ...
This enhances natural and antibody dependent cellular cytotoxicity. Lenalidomide and pomalidomide are about 100-1000 times more ... They have also been shown to cause dose dependent G0/G1 cell cycle arrest in leukemia cell lines where the analogs showed 100 ... Orphan indications include diffuse large B-cell lymphoma, chronic lymphocytic leukemia and mantle cell lymphoma. Lenalidomide ... is induced in the presence of TNF-α and the adhesion of MM cells to BMSC. In vitro proliferation of MM cell lines and ...
Olszewski MB, Groot AJ, Dastych J, Knol EF (May 2007). "TNF trafficking to human mast cell granules: mature chain-dependent ... "Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia". Nature 330 (6149): 662-64. Bibcode: ... "Lymphocyte in vitro cytotoxicity: characterization of human lymphotoxin". Proc. Natl. Acad. Sci. U.S.A. 61 (4): 1250-5. ... TNF Trafficking to Human Mast Cell Granules: Mature Chain-Dependent Endocytosis Olszewski et al., The Journal of Immunology, ...
Király R, Demény M, Fésüs L (December 2011). "Protein transamidation by transglutaminase 2 in cells: a disputed Ca2+-dependent ... Endomysial antibodies. *A collection of substrates and interaction partners of TG2 is accessible in the TRANSDAB, an ... "A role for tissue transglutaminase in alpha-gliadin peptide cytotoxicity". Clinical and Experimental Immunology. 146 (3): 550- ... cell membrane. • extracellular matrix. • collagen-containing extracellular matrix. Biological process. • apoptotic cell ...
protection from natural killer cell mediated cytotoxicity. • type I interferon signaling pathway. • immune response. • ... 1cg9: COMPLEX RECOGNITION OF THE SUPERTYPIC BW6-DETERMINANT ON HLA-B AND-C MOLECULES BY THE MONOCLONAL ANTIBODY SFR8-B6 ... antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent. • regulation of interleukin-12 ... positive regulation of T cell mediated cytotoxicity. • antigen processing and presentation of endogenous peptide antigen via ...
Antibody-dependent cell-mediated cytotoxicity: Antibodies attached to target cell cause destruction by macrophages, eosinophils ... Gamma delta T cellsEdit. Main article: Gamma delta T cell. Gamma delta T cells (γδ T cells) possess an alternative T cell ... antibody responses, and cell-mediated immune response. In antibody responses, B cells are activated to secrete antibodies, ... Like the T cell, B cells express a unique B cell receptor (BCR), in this case, a membrane-bound antibody molecule. All the BCR ...
"Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression". Virus Research. 149 (1 ... these mice demonstrated a deficiency in the maturation of an antibody response; they were able to generate normal levels of IgM ... HeLa cells are an immortalized cancer cell line used frequently in research. The cell line was established by removing cells ... leading to cell death. Cell death in organisms is necessary for the normal development of cells and the cell cycle maturation.[ ...
Antibody-dependent cell-mediated cytotoxicity[edit]. Infected cells are routinely opsonized with antibodies for detection by ... The contribution of antibody-dependent cell-mediated cytotoxicity to tumor cell killing can be measured with a specific test ... NK cells are thought to be an important cell type in this process.[17] These cells are known as "uterine NK cells" (uNK cells) ... CD16 (FcγIIIA) plays a role in antibody-dependent cell-mediated cytotoxicity; in particular, they bind IgG. ...
Cells are formed through mitosis at the basale layer. The daughter cells (see cell division) move up the strata changing shape ... Ultraviolet radiation (UVR) slightly damages the surface of skin and causes a time-dependent defect allowing easier penetration ... Skin with high permeability allowed quantum dots with an antibody attached to the surface for active targeting to successfully ... "Increased in vivo skin penetration of quantum dots with UVR and in vitro quantum dot cytotoxicity". Colloidal Quantum Dots for ...
The Adaptive Immune System: Ways That Antibodies Help to Defend the Body - Antibody-Dependent Cellular Cytotoxicity (ADCC) ... A parent cell divides to form two daughter cells, and these daughter cells are used to build new tissue, or to replace cells ... Cancer cells are cells that divide relentlessly, forming solid tumors or flooding the blood with abnormal cells. Cell division ... Stem cell research suggests that excess SP2 protein may turn stem cells into cancer cells.[7] However, a lack of particular co- ...
Disse Vörgang warrt ok „Antibody-dependent cell-mediated cytotoxicity" (ADCC) nöömt.. *As dat twee Binnensteden op en ... Dübel, S. (ed.) (2007) Handbook of Therapeutic Antibodies. Three Vol., 1160pages. Wiley-VCH, Weinheim, ISBN 978-3-527-31453-9. ...
... hydroxyphenyl and/or pyridiniumyl functional groups exhibit varying cytotoxicity to cancer cells in vitro, depending on the ... The efficiency of Type-II processes is dependent upon the triplet state lifetime τT and the triplet quantum yield (ΦT) of the ... Strategies include directly attaching photosensitisers to biologically active molecules such as antibodies.[5] ... However, this controlled feedback can be by-passed by artificially adding excess exogenous ALA to cells. The cells respond by ...
Selective cytotoxicity[edit]. Oleocanthal is capable of killing a variety of human cancer cells in vitro while leaving healthy ... Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose-dependent manner ... as well a potential monoclonal antibody against HGF and c-Met. ... Cells are forced into cell cycle arrest during G1 phase, ... the containers that store the cell's waste products, releasing enzymes that kill the cell. In healthy cells, the application of ...
They cause thyroid cell damage by complement activation and antibody dependent cell cytotoxicity.[7] However, anti-TPO ... The production of antibodies in Graves' disease is thought to arise by activation of CD4+ T-cells, followed by B-cell ... These B-cells produce antibodies specific to the thyroid antigens. In Hashimoto's thyroiditis, activated CD4+ T-cells produce ... anti-TPO antibodies, TPOAb), thyrotropin receptor antibodies (TRAb) and thyroglobulin antibodies (TgAb). TRAb's are subdivided ...
It is used to treat conditions resulting from overactivity of the B-cell-mediated antibody response. Examples include ... cell surface expression and function of human natural cytotoxicity receptors (NKp46, NKp44 and NKp30)". Clinical and ... Omega-3 fatty acids have a dose-dependent effect[70] in slightly reducing cortisol release influenced by mental stress,[71] ... alpha by antigen-presenting cells (APCs) and T helper (Th)1 cells, but upregulates IL-4, IL-10, and IL-13 by Th2 cells. This ...
It was discovered that gap junction communication could be disrupted by adding anti-connexin antibodies into embryonic cells.[ ... Many of those affect the skin because this tissue is heavily dependent upon gap junction communication for the regulation of ... "The extent of heterocellular communication mediated by gap junctions is predictive of bystander tumor cytotoxicity in vitro" ... "eat-5 and unc-7 represent a multigene family in Caenorhabditis elegans involved in cell-cell coupling". J. Cell Biol. 134 (2): ...
... and antibody class switching by B cells,[8] are division dependent. Sophisticated mathematical models have also been developed ... "An in vivo cytotoxicity threshold for influenza A virus-specific effector and memory CD8(+) T cells". Journal of Immunology ... "High-resolution tracking of cell division suggests similar cell cycle kinetics of hematopoietic stem cells stimulated in vitro ... By the use of fluorescent antibodies against different lymphocyte cell surface markers it is also possible to follow the ...
... a polarization of B cells that augments its therapeutic function in NK-cell-mediated antibody-dependent cellular cytotoxicity ... A monoclonal antibody for B cell non Hodgkin lymphoma and other affections.»։ Crit Rev Oncol Hematol 97: 275-290։ PMID 26443686 ... Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis»։ N Engl J Med 350 (25): 2572-81։ 2004 ... 5,0 5,1 Bosch Xavier, Ramos-Casals Manuel, Khamashta Munther A. (2013)։ Drugs Targeting B-Cells in Autoimmune Diseases ( ...
... and then by inducing antibody-dependent cellular cytotoxicity to eliminate remaining tumor cells.[47] A 3-day treatment course ... It works in two ways, first by disrupting cell membranes and mitochondria resulting cell death, ... These cells have been observed to proliferate into the dermis as buds and duct-like structures.[22] ... Moy, RL (Jan 2000). "Clinical presentation of actinic keratoses and squamous cell carcinoma". Journal of the American Academy ...
IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells". ... and reprogram the tumor microenvironment toward more effective dendritic cell activation and immune effector cell cytotoxicity. ... cause the B-cell to produce antibodies that help opsonisation of the antigen so that the bacteria can be better cleared by ... Once a T cell has recognized its particular antigen on the surface of an aberrant cell, the T cell becomes an activated ...
It was discovered that gap junction communication could be disrupted by adding anti-connexin antibodies into embryonic cells.[ ... "The extent of heterocellular communication mediated by gap junctions is predictive of bystander tumor cytotoxicity in vitro" ... "eat-5 and unc-7 represent a multigene family in Caenorhabditis elegans involved in cell-cell coupling". J. Cell Biol. 134 (2): ... When cells are compromised due to disease or injury and start to die messages are transmitted to neighboring cells connected to ...
Ligation of FcαRI by IgA containing immune complexes causes antibody-dependent cell-mediated cytotoxicity (ADCC), degranulation ... Production of sIgA against specific antigens depends on sampling of M cells and underlying dendritic cells, T cell activation, ... It binds to the polymeric immunoglobulin receptor on the basolateral surface of epithelial cells, and is taken up into the cell ... Immunoglobulin A (IgA, also referred to as sIgA in its secretory form) is an antibody that plays a crucial role in the immune ...
... Kory L. Alderson1,2 and Paul M. Sondel1, ... cells are powerful effector cells that can be directed to eliminate tumor cells through tumor-targeted monoclonal antibodies ( ... Therefore more research is needed that focuses on evaluating which NK cell and tumor criteria are best predictive of a clinical ... Strategies to augment the antitumor response by NK cells have led to an increased understanding of how to improve their ...
... is a mechanism of cell-mediated immunity whereby an effector ... Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) is a ... Antibody-dependent cell-mediated cytotoxicity Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) ... It uses material from the Wikipedia article "Antibody-dependent_cell-mediated_cytotoxicity". A list of authors is available in ... ADCC by NK cells. The typical ADCC involves activation of NK cells and is dependent on the recognition of antibody-coated ...
Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important biological function attributed to the mechanism of action ... Development and validation of an antibody-dependent cell-mediated cytotoxicity-reporter gene assay.. Parekh BS1, Berger E, ... Development and validation of an antibody-dependent cell-mediated cytotoxicity-reporter gene assay ... Development and validation of an antibody-dependent cell-mediated cytotoxicity-reporter gene assay ...
Nonneutralizing antibodies were poor inducers and did not inhibit antibody-dependent cell-mediated cytotoxicity. Interestingly ... antibody specificity profoundly influences the induction of antibody-dependent cell-mediated cytotoxicity by effector cells. In ... anti-neuraminidase antibodies weakly induced antibody-dependent cell-mediated cytotoxicity and enhanced induction in the ... Epitope specificity plays a critical role in regulating antibody-dependent cell-mediated cytotoxicity against influenza A virus ...
ADCC pathway activation by target cell-bound antibodies is achieved via FcgRIV-mediated NFAT activation and consequent ... induction of reporter luciferase activity in dual engineered Jurkat effector cells. ... Development of a Murine FcgRIV-Specific Antibody-Dependent Cell-mediated Cytotoxicity Reporter Assay Poster. ... ADCC pathway activation by target cell-bound antibodies is achieved via FcgRIV-mediated NFAT activation and consequent ...
Antibody-Dependent Cell Cytotoxicities. The phenomenon of antibody-mediated target Cell destruction by non-sensitized effector ... The effector Cell is a "killer" Cell possessing Fc Receptors. It may be a Lymphocyte lacking conventional B- or T-Cell markers ... The identity of the target Cell varies, but it must possess surface Immunoglobulin G whose Fc portion is intact. ... or a Monocyte, Macrophage, or polynuclear Leukocyte, depending on the identity of the target Cell. The reaction is Complement- ...
Potentiation of Antibody-Dependent Cell-Mediated Cytotoxicity by Target Cell-Bound C3b. Berhane Ghebrehiwet, Rudolf G. Medicus ... Potentiation of Antibody-Dependent Cell-Mediated Cytotoxicity by Target Cell-Bound C3b ... Identification and Separation of Thy-1 Positive Mouse Spleen Cells Active in Natural Cytotoxicity and Antibody-Dependent Cell- ... Potentiation of Antibody-Dependent Cell-Mediated Cytotoxicity by Target Cell-Bound C3b ...
... cells are powerful effector cells that can be directed to eliminate tumor cells through tumor-targeted monoclonal antibodies ( ... Clinical cancer therapy by NK cells via antibody-dependent cell-mediated cytotoxicity J Biomed Biotechnol. 2011;2011:379123. ... cells are powerful effector cells that can be directed to eliminate tumor cells through tumor-targeted monoclonal antibodies ( ... Therefore more research is needed that focuses on evaluating which NK cell and tumor criteria are best predictive of a clinical ...
CGD phagocytic cells (neutrophils and monocytes) had depressed ADCC acti … ... of leukocyte effector cells (neutrophils, lymphocytes, and monocytes) from normal subjects and from chronic granulomatous ... The present study characterized the antibody-dependent cellular cytoxicity (ADCC) ... Mechanisms of antibody-dependent cellular cytotoxicity: the use of effector cells from chronic granulomatous disease patients ...
Possible Evidence for Antibody-Dependent Macrophage-Mediated Cytotoxicity Directed against Murine Adenocarcinoma Cells in Vivo ... Possible Evidence for Antibody-Dependent Macrophage-Mediated Cytotoxicity Directed against Murine Adenocarcinoma Cells in Vivo ... Possible Evidence for Antibody-Dependent Macrophage-Mediated Cytotoxicity Directed against Murine Adenocarcinoma Cells in Vivo ... Possible Evidence for Antibody-Dependent Macrophage-Mediated Cytotoxicity Directed against Murine Adenocarcinoma Cells in Vivo ...
... dependent cell‐mediated cytotoxicity (ADCC) is an immunologic cytotoxic effector mechanism that is dependent on the cooperative ... Antibodydependent cell‐mediated cytotoxicity (ADCC) is an immunologic cytotoxic effector mechanism that is dependent on the ... 51Cr Release Assay of AntibodyDependent Cell‐Mediated Cytotoxicity (ADCC). David L. Nelson1, Carole C. Kurman1, Deborah E. ... Antibody‐coated and non‐antibody‐coated 51Cr‐labeled target‐cell (e.g., Chang‐cell) suspensions in complete RPMI‐10 medium (1 ...
Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers. AIDS 23:897- ... Antibody-Dependent Cell-Mediated Cytotoxicity in Simian Immunodeficiency Virus-Infected Rhesus Monkeys. Yue Sun, Mohammed Asmal ... HIV-1 gp120-specific antibody-dependent cell-mediated cytotoxicity correlates with rate of disease progression. J. Immunol. 157 ... Antigenic specificity of antibody-dependent cell-mediated cytotoxicity directed against human immunodeficiency virus in ...
... which can replace NK cells or PBMCs in such a cellular assays, based on Jurkat cells that stably express human FcγRIIIa (CD16a ... Build up a cellular ADCC screening system with BPS Biosciences reporter cell lines, ... ADCC Antibody-dependent cell-mediated cytotoxicity CD16 Fc receptor FcγRIIIa Natural killer cells NK cells ... Antibodies bind to specific antigens on the surface of the target cell (see Fig 1). PBMCs or natural killer (NK) cells, express ...
Traditional pharmacological studies done in cell monolayers have limited translational value; because, they do not capture the ... The need for biologically relevant assays with clinical translatability has brought the 3D cell culture model to the forefront ... Application Note: The Use of Elplasia™ Microplates for Antibody-Dependent Cell Mediated Cytotoxicity (ADCC) Applications. 6 ... the suitability of Kurarays Elplasia Square Type plates for antibody-dependent cell mediated cytotoxicity assays, using 3D ...
... ... antibody-dependent cell cytotoxicity (ADCC), as well as autoantibody levels, were quantified in plasma from 22 controllers and ... Regardless of the type of antibody tested, there was no correlation with HIV-specific CD8 T cell responses. ADCC was detectable ... The levels of these different antibody responses and HIV-specific CD8 T cell responses quantified by enzyme-linked ...
Elements Related to Heterogeneity of Antibody-Dependent Cell Cytotoxicity in Patients Under Trastuzumab Therapy for Primary ... Elements Related to Heterogeneity of Antibody-Dependent Cell Cytotoxicity in Patients Under Trastuzumab Therapy for Primary ... Elements Related to Heterogeneity of Antibody-Dependent Cell Cytotoxicity in Patients Under Trastuzumab Therapy for Primary ... Elements Related to Heterogeneity of Antibody-Dependent Cell Cytotoxicity in Patients Under Trastuzumab Therapy for Primary ...
Tetherin antagonism by Vpu protects HIV-infected cells from antibody-dependent cell-mediated cytotoxicity. Proc Natl Acad Sci U ... Antibody-dependent cellular cytotoxicity against reactivated HIV-1-infected cells. J Virol 90:2021-2030. doi:10.1128/JVI.02717- ... Antibody-dependent cell-mediated cytotoxicity in simian immunodeficiency virus-infected rhesus monkeys. J Virol 85:6906-6912. ... Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses. ...
Antibody-Dependent Cellular Cytotoxicity of Anti-CD20 IgG1 Fucose Variants against B Lymphoma Cell Lines with Differential CD20 ... Antibody-Dependent Cellular Cytotoxicity of IgG1 Fucose Variants against Experimental Target Cells with Various Antigen ... Enhanced Natural Killer Cell Binding and Activation by Low-Fucose IgG1 Antibody Results in Potent Antibody-Dependent Cellular ... Enhanced Natural Killer Cell Binding and Activation by Low-Fucose IgG1 Antibody Results in Potent Antibody-Dependent Cellular ...
We measured antibody-dependent cell mediated cytotoxicity (ADCC) activity in serum and genital fluids of heterosexually exposed ... 1987) Antibody-dependent cell-mediated cytotoxicity against cells infected with the human immunodeficiency virus. J Infect Dis ... 2011) Antibody-dependent cell cytotoxicity synapses form in mice during tumor-specific antibody immunotherapy. Cancer research ... 2014) Comparison of antibodies that mediate HIV type 1 gp120 antibody-dependent cell-mediated cytotoxicity in asymptomatic HIV ...
Semi-Automation of a Non-Radioactive Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Assay (Part I) ... Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) is part of a host immune defense where an effector cell of the immune ... One of the most common effector cell types is natural killer (NK) cells. Antibodies recruit effector cells such as NK cells ... Semi-Automation of a Non-Radioactive Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Assay (Part I) Download ...
1996) Interleukin-12 administered in vivo decreases human NK cell cytotoxicity and antibody dependent cytotoxicity to human ... 1993) Natural killer cytotoxicity and antibody dependent cellular cytotoxicity of human immunodeficiency virus-infected cells ... Target cells were K562 cells, and the assay ran for 3 h. Cells from healthy adults were tested at an effector cell:target cell ... and adult mononuclear cells (MNCs) in both natural killer (NK) cell and antibody-dependent cellular cytotoxicity (ADCC) assays ...
... and it inhibits IL-5-mediated cell proliferation. MEDI-563 potently induces antibody-dependent cell-mediated cytotoxicity of ... and it inhibits IL-5-mediated cell proliferation. MEDI-563 potently induces antibody-dependent cell-mediated cytotoxicity of ... Primary human eosinophils and basophils were used to demonstrate antibody-dependent cell-mediated cytotoxicity. The binding ... CONCLUSIONS: MEDI-563 might provide a novel approach for the treatment of asthma through active antibody-dependent cell- ...
NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity. Elife 7:e36806. ... CD16 is an Fc receptor that allows NK cells to detect and directly kill antibody-coated target cells through antibody-dependent ... The target cells were either K562 cells at a 1:1 ratio (PBMCs to K562 cells) or P815 cells at a 2:1 ratio (PBMCs to P815 cells ... B cells, NK cells, NKT cells, activated monocytes, and dendritic cells (17). The role of PD-1 in regulating T cell responses ...
Given the importance of antibody-dependent cellular cytotoxicity (ADCC) in the antitumor effect of trastuzumab and the ... but did not alter natural killer cells cytotoxicity. Preincubation of breast cancer cells with the conditioned medium derived ... The inhibition of ADCC was not due to titration or degradation of the antibody. We found that adipose cells decreased the ... Using a transcriptomic approach, we found that cancer cells undergo major modifications when exposed to adipocyte-conditioned ...
... were used to target immunologically activated effector cells in an in vitro antibody dependent cell mediated cytotoxicity (ADCC ... cells. Antibodies may also be used to broaden the range of tumor types susceptible to immune mediated cytotoxicity by the ... Each of these mAB was able to mediate ADCC with fresh effector cells and antibody binding targets. When peripheral blood ... The cells responsible for this ADCC had the CD16+ Fc receptor. Combining IL-2 with mAB in clinical tumor therapy may lead to a ...
Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells. ... Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells ... Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells ... Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells ...
NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC), triggered through ... Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic ... role for KIR-HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody- ... This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent ...
Antibodies, Viral Antibody-Dependent Cell Cytotoxicity Antibody Formation Antigenic Drift Article Child Child, Preschool ... Antibody-dependent cell-mediated cytotoxicity antibody responses to inactivated and live-attenuated influenza vaccination in ... Antibody-dependent cell-mediated cytotoxicity antibody responses to inactivated and live-attenuated influenza vaccination in ... may be more broadly cross-reactive and still protect through mechanisms including antibody-dependent cell-mediated cytotoxicity ...
Antibody-dependent cell-mediated cytotoxicity[edit]. Infected cells are routinely opsonized with antibodies for detection by ... The contribution of antibody-dependent cell-mediated cytotoxicity to tumor cell killing can be measured with a specific test ... NK cells are thought to be an important cell type in this process.[17] These cells are known as "uterine NK cells" (uNK cells) ... CD16 (FcγIIIA) plays a role in antibody-dependent cell-mediated cytotoxicity; in particular, they bind IgG. ...
... including neutralizing antibodies and antibodies with antibody-dependent cellular cytotoxic activity specific for GP. This is ... The vaccine elicited a variety of antibody responses to both antigens, ... Antibody-dependent cell-mediated cytotoxicity (ADCC). The ADCC activity of EBOV GP-specific IgG was quantified with an EBOV- ... A new cell line for high throughput HIV-specific antibody-dependent cellular cytocicity (ADCC) and cell-to-cell virus ...
  • Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) is a mechanism of cell-mediated immunity whereby an effector cell of the immune system actively lyses a target cell that has been bound by specific antibodies. (bionity.com)
  • ADCC is part of the adaptive immune response due to its dependence on a prior antibody response. (bionity.com)
  • The typical ADCC involves activation of NK cells and is dependent on the recognition of antibody-coated infected cells by Fc receptors on the surface of the NK cell. (bionity.com)
  • The interaction of the FcєRI receptor with the Fc portion of helminth bound IgE causes the eosinophil to release these granules in a mechanism similar to that of the NK cell during ADCC. (bionity.com)
  • Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important biological function attributed to the mechanism of action of several therapeutic antibodies, particularly oncology targeting mAbs. (nih.gov)
  • This data demonstrates that the ADCC-reporter gene assay has performance characteristics (accuracy, precision and robustness) to be used not only as a potency assay for lot release and stability testing for antibody therapeutics, but also as a key assay for the characterization and process development of therapeutic molecules. (nih.gov)
  • A) Anti-CD20 isotype antibodies mediated ADCC. (nih.gov)
  • Employing a model system consisting of 51 Cr-labeled chicken erythrocytes and purified human peripheral lymphocytes, we investigated the effect of target cell bound C3b on antibody-dependent cellular cytotoxicity (ADCC). (jimmunol.org)
  • At concentrations of anti-target cell antibody too low to cause effective ADCC, target cell bound C3b cooperated with antibody to produce marked target cell lysis. (jimmunol.org)
  • C3b-dependent enhancement of ADCC was dose dependent. (jimmunol.org)
  • The present study characterized the antibody-dependent cellular cytoxicity (ADCC) of leukocyte effector cells (neutrophils, lymphocytes, and monocytes) from normal subjects and from chronic granulomatous disease (CGD) patients. (nih.gov)
  • CGD phagocytic cells (neutrophils and monocytes) had depressed ADCC activity against antibody-coated human erythrocyte (HRBC) targets in suspension cultures indicative of abnormal intracellular postphagocytic killing. (nih.gov)
  • However, when phagocytosis was prevented by using a monolayer of antibody-coated HRBC targets, CGD monocytes, neutrophils, and lymphocytes exhibited normal ADCC activity. (nih.gov)
  • Thus, standard ADCC against HRBC targets in suspension is predominantly indicative of postphagocytic killing and, as such, is dependent upon a normal post-phagocytic respiratory burst of oxidative metabolism which is deficient in CGD neutrophils and monocytes. (nih.gov)
  • Hence, by employing CGD leukocytes as investigative probes in ADCC, fundamental mechanisms of intracellular vs. extracellular expression of cytotoxicity have been delineated. (nih.gov)
  • Antibody‐dependent cell‐mediated cytotoxicity (ADCC) is an immunologic cytotoxic effector mechanism that is dependent on the cooperative interaction of humoral and cellular effector elements. (currentprotocols.com)
  • This unit describes an assay of ADCC activity that can be used as a test for immunocompetence in effector cells or to test the activity of a monoclonal antibody to mediate ADCC. (currentprotocols.com)
  • Therefore, an ADCC assay involves three essential components: labeled target cells, antibodies with specificity for target‐cell surface antigens, and effector‐cell populations. (currentprotocols.com)
  • The basic protocol describes a method of measuring ADCC effector activity in lymphoid cells (peripheral blood mononuclear cells, or PBMC) that employs 51 Cr‐labeled target cells. (currentprotocols.com)
  • In the current study, we evaluated the kinetics of the antibody-dependent cell-mediated cytotoxicity (ADCC) response during acute and chronic SIVmac251 infection of rhesus monkeys. (asm.org)
  • We first adapted a flow cytometry-based ADCC assay, evaluating the use of different target cells as well as different strategies for quantitation of activated natural killer (NK) cells. (asm.org)
  • We also showed that ADCC responses can be detected as early as 3 weeks after SIVmac251 infection and that the magnitude of this antibody response is inversely associated with plasma viral RNA levels in animals with moderate to high levels of viral replication. (asm.org)
  • However, we also demonstrated an association between NK cell-mediated ADCC responses and the amount of SIVmac251 gp140 binding antibody that developed after viral infection. (asm.org)
  • This final observation raises the possibility that the antibodies that mediate ADCC are a subset of the antibodies detected in a binding assay and arise within weeks of infection. (asm.org)
  • These mechanisms include opsonization of viral particles for elimination by phagocytic cells or targeting of virus for destruction by antibody-dependent cell-mediated cytotoxicity (ADCC). (asm.org)
  • ADCC is an natural killer (NK) cell-mediated destruction of virus-infected cells that are targeted for destruction by antiviral antibodies. (asm.org)
  • The most formidable obstacle encountered in attempting to establish an ADCC assay is the selection of an appropriate way to express viral antigen on the surface of target cells. (asm.org)
  • Generally accepted targets for ADCC are either virus-infected, mitogen-stimulated peripheral blood mononuclear cells (PBMC) ( 18 ) or an immortalized cell line ( 26 ). (asm.org)
  • ADCC is a simple but important mechanism for the immune system to target diseased or infected cells. (tebu-bio.com)
  • ADCC is not only a natural part of the adaptive immune response, but animal experiments have shown that it can also be seen as an important mechanism of action of therapeutic monoclonal antibodies (1), including the breast cancer drug trastuzumab, and rituximab, a drug used to treat diseases which show overactive, dysfunctional, or excessive numbers of B cells (e.g. lymphomas). (tebu-bio.com)
  • To enable researchers to build up a cellular ADCC screening system, BPS Biosciences have developed 2 reporter cell lines, which can replace NK cells or PBMCs in such a cellular assay (see Fig 2). (tebu-bio.com)
  • The effectiveness of ADCC depends on how well the effector cells are activated after the engagement of FcγRIIIa. (tebu-bio.com)
  • BPS offers 2 different ADCC cell lines expressing either of these Fc receptors to allow selective antibody binding analyses using each type of receptor. (tebu-bio.com)
  • Get more information about our ADCC cell lines - just leave your questions or comments in the form below! (tebu-bio.com)
  • Neutralizing Antibody (nAb) activities (neutralization assay, competition with broadly reactive monoclonal antibodies, and reactivity against the viral MPER gp41 region), FcγR-mediated antiviral activities, antibody-dependent cell cytotoxicity (ADCC), as well as autoantibody levels, were quantified in plasma from 22 controllers and from viremic individuals. (ovid.com)
  • Rather, for most antibody types, controllers had the same or lower levels of nAbs than viremic individuals, with the possible exception of ADCC antibodies. (ovid.com)
  • Preliminary results from a pilot trial on trastuzumab's mechanism of action against operable breast tumors overexpressing Her2 suggested a role for antibody-dependent cell cytotoxicity (ADCC). (aacrjournals.org)
  • To examine factors affecting ADCC intensity and variability, we extended this study to the phenotypic and functional analysis of circulating mononuclear cells in 18 patients. (aacrjournals.org)
  • Phenotypic analysis at the end of ADCC evaluating down-regulation of CD16, and up-regulation of CD69 and CD107a, confirmed that natural killer (NK) cells and CD56 + T cells were involved in productive engagement of trastuzumab. (aacrjournals.org)
  • Also, the killing efficiency of CD16 + lymphocytes was influenced by 158 V/F polymorphism of FcγRIII (CD16), whereas variations of CD247 on NK cells were consistent with trends between ADCC before and after therapy. (aacrjournals.org)
  • HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cellular-mediated cytotoxicity (ADCC). (asm.org)
  • HIV-1 has evolved sophisticated mechanisms to avoid the exposure of Env ADCC epitopes by downregulating CD4 and by limiting the overall amount of Env on the cell surface. (asm.org)
  • Recent studies have revealed that fucose removal from the oligosaccharides of human IgG1 antibodies results in a significant enhancement of antibody-dependent cellular cytotoxicity (ADCC) via improved IgG1 binding to FcγRIIIa. (aacrjournals.org)
  • In this report, we investigated the relationship between enhanced ADCC and antigen density on target cells using IgG1 antibodies with reduced fucose. (aacrjournals.org)
  • Using EL4 cell-derived transfectants with differential expression levels of exogenous human CC chemokine receptor 4 or human CD20 as target cells, ADCC of fucose variants of chimeric IgG1 antibodies specific for these antigens were measured. (aacrjournals.org)
  • We further investigated IgG1 binding to natural killer (NK) cells and NK cell activation during ADCC induction to elucidate the mechanism by which low-fucose IgG1 induces ADCC upon target cells with low antigen expression. (aacrjournals.org)
  • The quantitative analysis revealed that fucose depletion could reduce the antigen amount on target cells required for constant degrees of ADCC induction by 10-fold for CC chemokine receptor 4 and 3-fold for CD20. (aacrjournals.org)
  • Our data showed that fucose removal from IgG1 could reduce the antigen amount required for ADCC induction via efficient recruitment and activation of NK cells. (aacrjournals.org)
  • Antibodies of the human IgG1 isotype are commonly used for therapeutic applications as they can mediate multiple effector functions including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct apoptosis induction (1-3) . (aacrjournals.org)
  • ADCC, a lytic attack on antibody-targeted cells, is triggered following binding of leukocyte receptors (FcγR) to the antibody Fc region. (aacrjournals.org)
  • Several mouse and clinical studies indicate that ADCC is an important therapeutic mechanism of clinically effective antibodies (4-7) . (aacrjournals.org)
  • FcγRIIIa is the predominant cγR of natural killer (NK) cells responsible for ADCC activation. (aacrjournals.org)
  • ADCC activity is influenced by the structure of complex-type oligosaccharides linked to CH2 domain of the antibody Fc region. (aacrjournals.org)
  • The content of galactose (12, 13) , bisecting N -acetylglucosamine (14, 15) , and fucose (16, 17) in the antibody oligosaccharide have each been reported to effect ADCC. (aacrjournals.org)
  • In previous studies, we have shown that fucose is the most critical antibody oligosaccharide component and that the removal of fucose from IgG1 oligosaccharides results in a very significant enhancement of both ADCC in vitro (∼100 fold) and antitumor activity in vivo (17, 18) . (aacrjournals.org)
  • Therefore, we generated a fucosyltransferase knockout Chinese hamster ovary cell line that can stably produce nonfucosylated antibodies with enhanced ADCC (19) that behaves in other respects indistinguishable from the parental line. (aacrjournals.org)
  • Background: We measured antibody-dependent cell mediated cytotoxicity (ADCC) activity in serum and genital fluids of heterosexually exposed women during HIV seroconversion. (omicsonline.org)
  • There is growing evidence that the HIV-specific antibodies whose activity is mediated through the Fc-receptor, such as antibody dependent cellular cytotoxicity (ADCC), have an important role in controlling HIV infection . (omicsonline.org)
  • ADCC antibodies can link virus-infected cells with effector cells (NK cells, monocytes and neutrophils) that can kill the infected cell and prevent further dissemination of the virus and disease progression. (omicsonline.org)
  • Further analysis of the results indicated that non-neutralizing antibodies, including antibodies that mediate ADCC against HIV, contributed significantly to the protection that was observed [ 2 - 6 ]. (omicsonline.org)
  • We investigated the ability of interleukin-2 (IL-2) and IL-12 to enhance the cytotoxicity of neonatal (cord blood) and adult mononuclear cells (MNCs) in both natural killer (NK) cell and antibody-dependent cellular cytotoxicity (ADCC) assays. (asm.org)
  • In ADCC assays with chicken erythrocyte targets, the combination of IL-2 and IL-12 increased the cytotoxicities of both cord blood and adult MNCs, with greater enhancement again seen with cord blood cells. (asm.org)
  • Incubation of cord blood cells, but not adult cells, with IL-2 or IL-12 for 1 week increased the percentage of CD16 + /CD56 + cells two- to fivefold and enhanced ADCC activity. (asm.org)
  • Thus, IL-2 and IL-12 greatly enhance both the NK cell and ADCC activities of neonatal MNCs and increase the number of NK cells in longer-term culture. (asm.org)
  • Newborn mononuclear cells (MNCs) have decreased antibody-dependent cellular cytotoxicity (ADCC) compared to the ADCC of MNCs from adults ( 11 , 12 ), and newborns have decreased numbers of NK cells with both CD16 and CD56, a phenotype associated with greater cytotoxicity ( 32 ). (asm.org)
  • Given the importance of antibody-dependent cellular cytotoxicity (ADCC) in the antitumor effect of trastuzumab and the abundance of adipose tissue in the breast, we investigated the impact of adipocytes on ADCC. (inserm.fr)
  • Results: We found that adipocytes, as well as preadipocytes, inhibited trastuzumab-mediated ADCC in HER2- expressing breast cancer cells via the secretion of soluble factors. (inserm.fr)
  • The inhibition of ADCC was not due to titration or degradation of the antibody. (inserm.fr)
  • Preincubation of breast cancer cells with the conditioned medium derived from adipocytes reduced the sensitivity of cancer cells to ADCC. (inserm.fr)
  • These mAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective mAb-mediated cancer therapies. (aacrjournals.org)
  • A fully human anti-PD-L1 mAb would potentially be able to block PD-1/PD-L1 interactions and also mediate the ADCC lysis of tumor cells. (aacrjournals.org)
  • and (vi) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. (aacrjournals.org)
  • These fully human or humanized mAbs are either of the IgG 4 isotype, which does not mediate antibody-dependent cell-mediated cytotoxicity (ADCC), or of the IgG 1 isotype and specifically engineered to eliminate ADCC activity. (aacrjournals.org)
  • This has been done to obviate any potential toxicity that may result from ADCC-mediated lysis of subsets of immune cells that express PD-L1. (aacrjournals.org)
  • Following the response of the adaptive immune system, NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC), triggered through cross-linking of the CD16 Fc receptor by donor-specific antibodies bound to allograft. (escholarship.org)
  • This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent role for KIR-HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody-mediated rejection of solid organ transplants. (escholarship.org)
  • Non-neutralizing antibodies may be more broadly cross-reactive and still protect through mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC). (cdc.gov)
  • Influenza vaccines may stimulate ADCC antibodies in adults, but whether they do so in children is unknown. (cdc.gov)
  • Here we examined how vaccination affects cross-reactive ADCC antibody responses in children after receipt of inactivated trivalent vaccine (IIV3) or quadrivalent live-attenuated vaccine (LAIV4). (cdc.gov)
  • Treatment of porcine lymphocytes with trypsin reduced their spontaneous cell-mediated cytotoxicity (SCMC) activity against target cells persistently infected with transmissible gastroenteritis virus (PK15-TGE cells), but had no effect on antibody-dependent cell-mediated cytotoxicity (ADCC). (islandscholar.ca)
  • Thus SCMC and ADCC mediated by porcine lymphocytes against PK15-TGE target cells clearly involved two distinct mechanisms in terms of antibody participation and sensitivity to trypsin. (islandscholar.ca)
  • Here we describe an automated impedance-based assay that in a real-time and label-free manner captures the kinetics of cell-mediated or antibody-dependent cell-mediated cytolysis (ADCC) of cancer cells. (biomedcentral.com)
  • Prospective monitoring of active Chronic Epstein-Barr virally infected patients receiving gammaglobulin therapy was performed using the antibody-dependent cell-mediated cytotoxicity assay (ADCC). (elsevier.com)
  • Antibody-dependent cellular cytotoxicity ( ADCC ), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose membrane-surface antigens have been bound by specific antibodies . (wikipedia.org)
  • ADCC is independent of the immune complement system that also lyses targets but does not require any other cell. (wikipedia.org)
  • ADCC requires an effector cell which classically is known to be natural killer (NK) cells that typically interact with immunoglobulin G (IgG) antibodies. (wikipedia.org)
  • [3] However, macrophages , neutrophils and eosinophils can also mediate ADCC, such as eosinophils killing certain parasitic worms known as helminths via IgE antibodies. (wikipedia.org)
  • The typical ADCC involves activation of NK cells by antibodies. (wikipedia.org)
  • Several laboratory methods exist for determining the efficacy of antibodies or effector cells in eliciting ADCC. (wikipedia.org)
  • By retaining a native Fc-region, avelumab is thought to potentially engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). (thefreedictionary.com)
  • Using Xencor's XmAb Fc enhancement technology, MOR208 has been engineered to possess significantly enhanced antibody-dependent cell-mediated cytotoxicity (ADCC), thus improving a key mechanism for tumour cell killing and offering potential for enhanced efficacy compared to traditional antibodies for the treatment of cancer. (thefreedictionary.com)
  • In addition to inhibitory properties, cetuximab has immunologic anti-tumor effects, and antibody-dependent cellular cytotoxicity (ADCC) activity, which has not been well studied. (elsevier.com)
  • In this study, we investigated the ADCC activity of cetuximab against colorectal cancer (CRC) cell lines. (elsevier.com)
  • We examined the correlation between EGFR expression in six CRC cell lines and ADCC activity of cetuximab. (elsevier.com)
  • Cetuximab showed no growth inhibitory effect in any of the cell lines, whereas it showed maximum ADCC activity at a very low concentration of 0.025 μg/ml. (elsevier.com)
  • In this study, tamoxifen was used to increase HER2/neu protein level to determine whether increased tumor antigen expression could enhance NK cell-mediated antibody-dependent cytotoxicity (ADCC). (aah.org)
  • Using flow cytometry to simultaneously evaluate NK cell degranulation and tumor cell death, the increase in HER2/neu enhanced NK cell-mediated ADCC. (aah.org)
  • The Ab-dependent cell-mediated cytotoxicity (ADCC) activity of anti-gp120 Abs in serum from four groups of HIV-1-positive individuals in the Multicenter AIDS Cohort Study was evaluated at several time points over a 10-yr period. (elsevier.com)
  • Among seroconverters who were nonrapid progressors, those with low or declining ADCC titers lost significantly more CD4 + cells during the study than those whose ADCC titers were stable or increasing, even though both groups had similar serum virion RNA levels. (elsevier.com)
  • Anti-HIV-1 envelope glycoprotein (Env) antibodies without broadly neutralizing activity correlated with protection in the RV144 clinical trial, stimulating interest in other protective mechanisms involving antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC). (duke.edu)
  • Env epitopes targeted by many antibodies effective at mediating ADCC are poorly exposed on the unliganded Env trimer. (duke.edu)
  • Here we investigated the mechanism of exposure of ADCC epitopes on Env and showed that binding of Env and CD4 within the same HIV-1-infected cell effectively exposes these epitopes. (duke.edu)
  • Importantly, cell surface CD4 downregulation by Nef and Vpu accessory proteins and Vpu-mediated BST-2 antagonism modulate exposure of ADCC-mediating epitopes and reduce the susceptibility of infected cells to this effector function in vitro. (duke.edu)
  • Altogether, our observations describe a highly conserved mechanism required to expose ADCC epitopes that might help explain the evolutionary advantage of downregulation of cell surface CD4 by the HIV-1 Vpu and Nef proteins.HIV-1 envelope epitopes targeted by many antibodies effective at mediating antibody-dependent cell-mediated cytotoxicity (ADCC) are poorly exposed on the unliganded envelope trimer. (duke.edu)
  • The anti-PD-L1 mAb avelumab is unique among checkpoint inhibitors in that it is a fully human IgG1 capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) of PD-L1-expressing tumor cells. (oncotarget.com)
  • We examined 4 chordoma cell lines, first for expression of PD-L1, and in vitro for ADCC killing using NK cells and avelumab. (oncotarget.com)
  • PD-L1 expression was markedly upregulated by IFN-γ in all 4 chordoma cell lines, which significantly increased sensitivity to ADCC. (oncotarget.com)
  • Co-incubating chordoma cells with brachyury-specific CD8 + T cells resulted in significant upregulation of PD-L1 on the tumor cells, mediated by the CD8 + T cells' IFN-γ production, and increased sensitivity of chordoma cells to avelumab-mediated ADCC. (oncotarget.com)
  • Residential cancer stem cell subpopulations of chordoma cells were also killed by avelumab-mediated ADCC to the same degree as non-cancer stem cell populations. (oncotarget.com)
  • These findings suggest that as a monotherapy for chordoma, avelumab may enable endogenous NK cells, while in combination with T-cell immunotherapy, such as a vaccine, avelumab may enhance NK-cell killing of chordoma cells via ADCC. (oncotarget.com)
  • Most PD-L1 inhibitors contain modified fragment crystallizable region (Fc) receptor binding sites to prevent antibody-dependent cellular cytotoxicity (ADCC) against PD-L1-expressing non-tumor cells. (bmj.com)
  • However, natural killer (NK) cells have specific antitumor activity in the presence of tumor-targeting antibody through ADCC, which could enhance NK cell-induced cytotoxicity. (bmj.com)
  • We evaluated the antitumor efficacy of ADCC via anti-PD-L1 monoclonal antibodies (mAbs) and NK cells against several PD-L1-positive cancer cell lines. (bmj.com)
  • Results We demonstrated that the cytotoxicity of NK-92-CD16 cells toward PD-L1-positive cancer cell lines was significantly enhanced in the presence of anti-PD-L1 mAb with ADCC. (bmj.com)
  • We also noted a significant increase in primary human NK cell cytotoxicity against PD-L1-positive human cancer cells when cocultured with anti-PD-L1 mAb with ADCC. (bmj.com)
  • Moreover, NK cells expressing a FCGR3A high-affinity genotype displayed higher anti-PD-L1 mAb-mediated ADCC lysis of tumor cells than donors with a low-affinity genotype. (bmj.com)
  • Conclusion These results suggest that NK cells induce an ADCC response in combination with anti-PD-L1 mAbs, which helps promote ADCC antitumor activity against PD-L1-positive tumors. (bmj.com)
  • This study provides support for NK cell immunotherapy against high PD-L1-expressing tumors in combination with ADCC through anti-PD-L1 mAbs. (bmj.com)
  • Here, a repertoire of mAbs against human CD5 was generated and tested for ability to induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) both as single mAbs and combinations of two mAbs against non-overlapping epitopes on human CD5. (forskningsdatabasen.dk)
  • Filling this cavity with a histidine or tryptophan residue in Env with a natural serine residue at this position (S375H/W) increased the susceptibility of HIV-1-infected cells to ADCC. (chavi-id.org)
  • Our results raise the intriguing possibility that the presence of His 375 in the circulating strain where the RV144 trial was held contributed to the observed vaccine efficacy.IMPORTANCE HIV-1-infected cells presenting Env in the CD4-bound conformation on their surface are preferentially targeted by ADCC mediated by HIV-positive (HIV(+)) sera. (chavi-id.org)
  • Here we show that the gp120 Phe 43 cavity modulates the propensity of Env to sample this conformation and therefore affects the susceptibility of infected cells to ADCC. (chavi-id.org)
  • Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response largely mediated by natural killer (NK) cells that can lyse target cells and combat tumors and viral infections. (ox.ac.uk)
  • We identified Fcε receptor-expressing cells, monocytes/macrophages and eosinophils, activated by MOv18 IgE to kill tumour cells by mechanisms such as ADCC and ADCP. (springer.com)
  • We examined the role of antibody-dependent cellular cytotoxicity (ADCC) using JIMT-1 cells that are ErbB2 positive but intrinsically resistant to trastuzumab in vitro . (aacrjournals.org)
  • Moreover, in vitro ADCC reaction of human leukocytes was equally strong against breast cancer cells intrinsically sensitive (SKBR-3) or resistant (JIMT-1) to trastuzumab or even against a subline of JIMT-1 that was established from xenograft tumors growing despite trastuzumab treatment. (aacrjournals.org)
  • Thus, measuring the ADCC activity of patient's leukocytes against the tumor cells may be a relevant predictor of clinical trastuzumab responsiveness in vivo . (aacrjournals.org)
  • In addition to the direct effects on cancer cells, several lines of evidence suggested that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in the antitumor activity of trastuzumab. (aacrjournals.org)
  • Human lymphocyte antibody-dependent cell-mediated cytotoxicity (ADCC) toward human red blood cells. (rochester.edu)
  • This phenomenon, recently reviewed by Perlmann , Perlmann , and Wigzell (1972), was first described by Möller in 1965 and has received a number of designations, including antibody-dependent cell-mediated (or cellular) cytotoxicity (ADCC), antibody-dependent lymphocyte cytotoxicity (ADLC), cell dependent antibody-mediated cytotoxicity (CDAMC), and lymphocyte-dependent antibody (LDA). (springer.com)
  • Antibody bound to soluble or membrane antigens can bind CD16 on NK cells leading to antibody-dependent cell cytotoxicity (ADCC) and secretion of IFN-γ and GM-CSF ( 8 , 9 ). (rupress.org)
  • 75. The method according to claim 65, wherein the antibody induces antibody-dependent cell-mediated cytotoxicity (ADCC). (freepatentsonline.com)
  • This is an IgG4 masking antibody that shows neither antibody-dependent cell-mediated cytotoxicity (ADCC) nor complement-dependent cytotoxicity (CDC) 27 . (pubmedcentralcanada.ca)
  • HIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. (biomedcentral.com)
  • The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. (biomedcentral.com)
  • The Sanger's method of sequencing was used to sequence the exon of FcγRIIIa receptor while the ADCC activity was determined using NK cell activation assay. (biomedcentral.com)
  • The polymorphism in FcγRIIIa receptor was assessed in HIV-infected Indian individuals with or without HIV-specific ADCC antibodies and its influence on the magnitude of HIV-specific ADCC responses was analyzed. (biomedcentral.com)
  • The study underscores the role of polymorphism in the FcγRIIIa receptor on HIV-specific ADCC response and suggests that the screening of the individuals for FcγRIIIa-V176F and Y158H polymorphisms could be useful for prediction of efficient treatment in monoclonal antibody-based therapies aimed at ADCC in HIV infection. (biomedcentral.com)
  • This polymorphism is in the exon 4 and is reported to alter the protein confirmation and thus influences binding affinity of FcγRIIIa and Fc region of antibodies involved in ADCC [ 14 , 21 ]. (biomedcentral.com)
  • Upon vaccination, naxitamab stimulates antibody-dependent cell-mediated cytotoxicity (ADCC) against GD2-expressing tumor cells. (cancer.gov)
  • Compared to the murine monoclonal antibody 3F8 (m3F8), the humanized form does not cause a human anti-mouse antibody (HAMA) response and shows enhanced ADCC activity. (cancer.gov)
  • Antibody‐dependent cell‐mediated cytotoxicity (ADCC) is the killing of an antibody‐coated target cell by a cytotoxic effector cell through a nonphagocytic process, characterised by the release of the content of cytotoxic granules or by the expression of cell death‐inducing molecules. (els.net)
  • ADCC is triggered through interaction of target‐bound antibodies (belonging to IgG or IgA or IgE classes) with certain Fc receptors (FcRs), glycoproteins present on the effector cell surface that bind the Fc region of immunoglobulins (Ig). (els.net)
  • ADCC involving human IgG1, the most used IgG subclass for therapeutic antibodies, is highly dependent on the glycosylation profile of its Fc portion and on the polymorphism of Fcγ receptors. (els.net)
  • Antibodies bound to target cells (virus‐infected or tumour cells) and Fc receptors expressed by cytotoxic cells are the major actors of ADCC. (els.net)
  • ADCC mechanisms that lead to target cell death vary depending on effector cells that are recruited by antibodies. (els.net)
  • FcγRIIa and FcγRIIIa polymorphism impact ADCC efficacy by IgG1 antibodies. (els.net)
  • Engineering FcIgG either by introducing point mutations or by modifying the glycosylation profile allows to optimise IgG1 antibodies for enhanced ADCC. (els.net)
  • Bispecific antibodies that bind activating molecules expressed by cytotoxic cells and tumour cells can mimic classical ADCC. (els.net)
  • Natural killer (NK) cells are powerful effector cells that can be directed to eliminate tumor cells through tumor-targeted monoclonal antibodies (mAbs). (hindawi.com)
  • Continued research into the antitumor effects induced by NK cells and tumor-targeted mAbs suggests that additional intrinsic and extrinsic factors may influence the antitumor response. (hindawi.com)
  • Therefore more research is needed that focuses on evaluating which NK cell and tumor criteria are best predictive of a clinical response and which combination immunotherapy regimens to pursue for distinct clinical settings. (hindawi.com)
  • Tumor cells from immune mice appear to be coated with this antibody, as they are sensitive to the effects of normal macrophages in vitro, whereas tumor cells from immunologically compromised mice are not. (jimmunol.org)
  • Thus, a macrophage-dependent reaction probably is relevant in the in situ immune defenses against this tumor. (jimmunol.org)
  • Natural killer (NK) cells are large granular lymphocytes capable of lysing many types of tumor and virus-infected cells without prior sensitization. (asm.org)
  • Monoclonal antibodies (mAB) with tumor specificity are able to enhance the immunological specificity of interleukin 2 (IL-2)-activated lymphokine activated killer (LAK) cells. (semanticscholar.org)
  • Antibodies may also be used to broaden the range of tumor types susceptible to immune mediated cytotoxicity by the activated LAK cells. (semanticscholar.org)
  • The mode of action of these mAbs is to inhibit PD-1 on immune cells interacting with PD-L1 on tumor cells. (aacrjournals.org)
  • Ipilimumab (anti-CTLA-4) has shown significant clinical benefit in metastatic melanoma ( 1 ), and several mAbs directed against programmed cell death protein-1 ligand (PD-L1) and PD-1 have demonstrated clinical benefit in patients with melanoma, Hodgkin lymphoma, lung and bladder carcinomas, and other tumor types ( 2-14 ). (aacrjournals.org)
  • The mode of action of these anti-PD-1/PD-L1 mAbs is to inhibit the interaction of PD-1 on immune cells with PD-L1 on tumor cells, thus reducing or eliminating immunosuppressive signals, and leading to enhanced immune cell activation. (aacrjournals.org)
  • It should be pointed out that although all of these mAbs have demonstrated clear clinical benefit, and have been approved by the FDA for their respective indications, all three target molecules are expressed on non-tumor cell populations. (aacrjournals.org)
  • Recognition of self-human leukocyte antigen (HLA) class I molecules by inhibitory killer cell immunoglobulin-like receptors (KIRs) is involved in the calibration of NK cell effector capacities during the developmental stage, allowing the subsequent recognition and elimination of target cells with decreased expression of self-HLA class I (due to virus infection or tumor transformation) or HLA class I disparities (in the setting of allogeneic transplantation). (escholarship.org)
  • NK cells provide rapid responses to virus-infected cells, acting at around 3 days after infection , and respond to tumor formation. (wikipedia.org)
  • However, as tumors progress, cancerous cells develop immunosuppressive mechanisms that circumvent NK cell-mediated killing, allowing for tumor escape and proliferation. (frontiersin.org)
  • Therapeutic intervention aims to reverse tumor-induced NK cell suppression and sustain NK cells' tumorlytic capacities. (frontiersin.org)
  • Here, we review tumor-NK cell interactions, discuss the mechanisms by which NK cells generate an antitumor immune response, and discuss NK cell-based therapeutic strategies targeting activating, inhibitory, and co-stimulatory receptors. (frontiersin.org)
  • instead of targeting tumor cells, the goal of immunotherapy is to augment and expand the immune system's intrinsic antitumor response. (frontiersin.org)
  • First described in 1975, NK cells were initially identified as a distinct sub-population of lymphocytes by their capacity to spontaneously lyse tumor cells ( 1 ). (frontiersin.org)
  • NK cells are now accepted to play an important role in both the adaptive and innate immune responses that govern infection, autoimmunity, and tumor immunosurveillance ( 2 , 3 ). (frontiersin.org)
  • Specifically, the xCELLigence system was used to monitor the response of tumor cells to natural killer (NK) cell activity in the presence or absence of an immunoglobulin G isotype-specific antibody. (biomedcentral.com)
  • Importantly, we show that the addition of NK cells in suspension over a monolayer of adherent tumor cells does not cause impedance changes because the NK cells do not come in contact with the electronic sensor. (biomedcentral.com)
  • However, in the presence of antibody these non-adherent NK cells inject perforins and granzymes into the tumor cells, causing apoptosis. (biomedcentral.com)
  • The resultant morphological changes, death, and detachment of the tumor cells are readily detected via changes in impedance. (biomedcentral.com)
  • The design of new generations of improved antibodies for immunotherapy should aim at Fc optimization to increase the engagement of activating FcγR present on the surface of tumor-infiltrating effector cell populations. (aacrjournals.org)
  • Immunotherapy of cancer with monoclonal antibodies (mAb) promotes elimination of tumor cells by a variety of mechanisms. (aacrjournals.org)
  • Experimental evidence includes a study in a reconstituted nonobese diabetic/severe combined immunodeficient tumor model of human adult T-cell leukemia, which showed that improved survival after anti-CD25 immunotherapy was associated with non-natural killer cell-mediated Fcγ-dependent tumor cell killing ( 1 ). (aacrjournals.org)
  • A distinct mechanism involving increased expression of X-linked inhibitor of apoptosis protein (XIAP) and survivin, key members of the inhibitor of apoptosis protein (IAP) family, was observed post-trastuzumab (an ErbB2 monoclonal antibody) treatment in an ErbB2-overexpressing, estrogen receptor negative, IBC cellular model, SUM190PT, isolated from a primary IBC tumor. (aacrjournals.org)
  • Furthermore, NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface, indicating a non-self cell. (wikipedia.org)
  • In addition, they produce several cytokines including interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF) ( 2 ) and chemokines (macrophage inflammatory protein (MIP)-1α (CCL3), MIP-1β (CCL4) and CCL5, also known as RANTES (regulated on activation, normal T cell expressed and secreted) ( 3 ). (frontiersin.org)
  • These cells, were named as natural killer cells because of their capacity to destroy tumor cells without prior sensitization ( 4 ). (frontiersin.org)
  • In addition to the antiviral immune response, NK cells are implicated in tumor surveillance. (frontiersin.org)
  • Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity in vitro. (thefreedictionary.com)
  • 1F5 activates T cells only in combination with T-cell receptor stimulation and does not induce proliferation of primary CD27-expressing tumor cells. (aacrjournals.org)
  • Tumor-targeting antibodies have been successful in the treatment of various types of cancers. (aah.org)
  • The quantity of HER2/neu on the tumor cell surface was approximately double that of the number of Fc receptors found on NK cells. (aah.org)
  • The cytotoxic activity of the NK-cells is controlled by the balance between inhibitory and activating receptors, whose ligands are self-Major Histocompatibility Complex (MHC) class I molecules and molecules expressed on stressed, viral infected, and tumor cells. (hindawi.com)
  • Human monocyte, lymphocyte, and granulocyte antibody-dependent cell-mediated cytotoxicity toward tumor cells. (rochester.edu)
  • Human monocyte antibody-dependent cell-mediated cytotoxicity to tumor cells. (rochester.edu)
  • Human monocyte cytotoxicity to tumor cells. (rochester.edu)
  • Non-T cell killing of mammary tumor cells by spleen cells: secretion of antibody and recruitment of cells. (springer.com)
  • Antibody in the sera of tumorbearing mice that mediates spleen cell cytotoxicity toward autologous tumor. (springer.com)
  • Cell-mediated cytotoxicity, allograft rejection and tumor immunity. (springer.com)
  • Cancer immunotherapy exploits the fact that cancer cells often have tumor antigens, molecules on their surface that can be detected by the antibody proteins of the immune system, binding to them. (wikipedia.org)
  • Normal antibodies bind to external pathogens, but the modified immunotherapy antibodies bind to the tumor antigens marking and identifying the cancer cells for the immune system to inhibit or kill. (wikipedia.org)
  • Active immunotherapy specifically targets tumor cells via the immune system. (wikipedia.org)
  • In contrast, passive immunotherapy does not directly target tumor cells, but enhances the ability of the immune system to attack cancer cells. (wikipedia.org)
  • In cell-mediated therapies like CAR-T cell therapy, immune cells are extracted from the patient, genetically engineered to recognize tumor specific antigens, and returned to the patient. (wikipedia.org)
  • Dendritic cell therapy provokes anti-tumor responses by causing dendritic cells to present tumor antigens to lymphocytes, which activates them, priming them to kill other cells that present the antigen. (wikipedia.org)
  • The only approved cellular cancer therapy based on dendritic cells is sipuleucel-T. One method of inducing dendritic cells to present tumor antigens is by vaccination with autologous tumor lysates or short peptides (small parts of protein that correspond to the protein antigens on cancer cells). (wikipedia.org)
  • FPA150 is designed with a dual mechanism of action: blocking the T cell checkpoint activity of B7-H4 as well as promoting enhanced antibody-dependent cell-mediated cytotoxicity against tumor cells expressing B7-H4. (thefreedictionary.com)
  • FPA150 has a dual mechanism of action: it blocks a T cell checkpoint pathway and delivers antibody-dependent cell-mediated cytotoxicity against B7-H4-expressing tumor cells. (thefreedictionary.com)
  • CAIX is expressed on the surface of most renal cancer cells and is hypothesized to be on the surface of other tumor cells. (wikipedia.org)
  • By binding to PD-L1, avelumab is thought to prevent tumor cells from using PD-L1 for protection against white blood cells, such as T cells, exposing them to anti-tumor responses. (newswire.ca)
  • The intent of vaccination is to induce a combined antibody and T-cell anti-HER-2 immune response, which is intended to target HER-2-expressing tumor cells, and may induce tumor regression or slow progression of disease. (stanford.edu)
  • The primary purpose of this study is to determine whether breast cancer tumors respond (as measured by pathologic complete response: the absence of microscopic evidence of invasive tumor cells in the breast) to combined chemotherapy of AC(doxorubicin and cyclophosphamide) followed by paclitaxel plus trastuzumab or lapatinib or both given before surgery to patients with HER2-positive breast cancer. (stanford.edu)
  • RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. (stanford.edu)
  • 65. A method for treating a solid tumor comprising administering to the human an effective amount of an anti-interleukin-1 receptor accessory protein (IL1RAP) antibody with specificity for an extracellular domain of human IL1RAP wherein cells of the solid tumor express IL1RAP. (freepatentsonline.com)
  • Co-administration of this agent with 5-FC and upon local activation of 5-FU in the brain tumor, 5-FU disrupts DNA synthesis in tumor cells thereby impeding cellular proliferation with minimal systemic exposure and toxicity. (cancer.gov)
  • A humanized monoclonal antibody directed against the human tumor-associated antigen GD2, with potential antineoplastic activity. (cancer.gov)
  • Although complement-dependent cytotoxicity, the interference with signaling pathways, or the induction of apoptosis have all been invoked, accumulated evidence suggests a major role for the engagement of Fc-γ receptors (FcγR) and the recruitment of effector cells in Fc-dependent cellular cytotoxicity events. (aacrjournals.org)
  • The assessment also included in vitro and in vivo complement-dependent cytotoxicity and antibody-dependent T cell-mediated cytotoxicity tests, and efficacy studies using a colon carcinoma model in a human CTLA-4 transgenic mouse. (thefreedictionary.com)
  • The Fc receptors recognize the Fc (crystalline) portion of antibodies such as IgG , which bind to the surface of a pathogen -infected target cell. (bionity.com)
  • The effector Cell is a "killer" Cell possessing Fc Receptors . (online-medical-dictionary.org)
  • Antibody-dependent cytolytic effector lymphocytes are known to possess, in part, receptors for activated C3. (jimmunol.org)
  • The antibody appears to be present in two forms, one apparently complexed with antigen and the other identified as 7S immunoglobulin on Sephadex G-200 and as the IgG2a subclass by blocking of Fc receptors on the macrophages. (jimmunol.org)
  • In this form of cytotoxicity, effector cells with receptors for the Fc portion of immunoglobulin produce target cell lysis by attachment to the Fc portion of antibodies that are bound to target cells via their antigen‐combining sites. (currentprotocols.com)
  • PBMCs or natural killer (NK) cells, express Fc receptors on their cell surface and act as the effector cells. (tebu-bio.com)
  • Importantly, several reports have recently shown that FCGR3A genotype influences the clinical efficacy of human IgG1-type anti-CD20 antibody rituximab (3, 10, 11) with the clinical response of patients bearing FcγRIIIa-158F being significantly inferior to the patients with the FcγRIIIa-158V receptors (5-7) . (aacrjournals.org)
  • NK cells also have Fc receptors (CD16) on their surfaces. (asm.org)
  • These receptors allow NK cells to kill antibody-coated target cells, thus providing another form of immune defense ( 12 , 35 ). (asm.org)
  • The Impact of HLA Class I-Specific Killer Cell Immunoglobulin-Like Receptors on Antibody-Dependent Natural Killer Cell-Mediated Cytotoxicity and Organ Allograft Rejection. (escholarship.org)
  • The cumulative activating and inhibitory signals generated by ligation of the receptors regulates mature NK cell killing of target cells and their production of cytokines and chemokines. (escholarship.org)
  • In contrast to NKT cells, NK cells do not express T-cell antigen receptors (TCR) or pan T marker CD3 or surface immunoglobulins (Ig) B cell receptors , but they usually express the surface markers CD16 (FcγRIII) and CD56 in humans, NK1.1 or NK1.2 in C57BL/6 mice . (wikipedia.org)
  • In addition to the knowledge that natural killer cells are effectors of innate immunity , recent research has uncovered information on both activating and inhibitory NK cell receptors which play important functional roles, including self tolerance and the sustaining of NK cell activity. (wikipedia.org)
  • NK cell receptors can also be differentiated based on function. (wikipedia.org)
  • Natural cytotoxicity receptors directly induce apoptosis after binding to Fas ligand that directly indicate infection of a cell. (wikipedia.org)
  • The MHC-dependent receptors (described above) use an alternate pathway to induce apoptosis in infected cells. (wikipedia.org)
  • NCR (natural cytotoxicity receptors), a type of type 1 transmembrane proteins of the immunoglobulin superfamily, upon stimulation, mediate NK killing and release of IFNγ. (wikipedia.org)
  • NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors. (frontiersin.org)
  • However, CD56 dim NK cells can produce cytokines, specifically IFN-γ, after cell triggering via NKp46 of NKp30 activating receptors or after stimulation with combinations of IL-2, IL-12, and IL-15 ( 7 ). (frontiersin.org)
  • Although the mechanism of action in vivo is not always known, the therapeutic activity of several approved mAbs depends on the binding of the Fcγ regions to low-affinity Fcγ receptors (FcγR) expressed on effector cells. (aacrjournals.org)
  • An NK cell expresses Fc receptors, mostly CD16 . (wikipedia.org)
  • Next, the NK cells which have Fc Receptors will bind to that antibody, inducing the NK cell to release proteins such as perforin and proteases known as granzymes , which causes the lysis of the infected cell to hinder the spread of the virus. (wikipedia.org)
  • NK cells constitute about 10% of the mononuclear cells in human peripheral blood and their function are regulated by a number of germline-encoded activating/inhibitory receptors that together orchestrate their activation ( 7 , 8 ). (frontiersin.org)
  • These receptors can be divided into three groups, (i) killer immunoglobulin-like receptors (KIRs), (ii) natural cytotoxicity receptors (NCR) and (iii) NKG2/CD94 heterodimer family (C-type Lectin-like receptors). (frontiersin.org)
  • In addition, NK cell surveys the expression of MHC class I molecules through inhibitory receptors like NKG2A and KIRs to protect healthy cells from NK cell-mediated killing. (frontiersin.org)
  • NK cells also express Toll-like receptors (TLRs), and in vitro assays shows that TLR agonists can activate them, revealing their role in early defense against other pathogens than the virus ( 11 ). (frontiersin.org)
  • This success is thought to be driven, in part, by the accessibility of these types of tumors to antibodies and immune effector cells, as well as the number of tissue-specific receptors that provide potential therapeutic targets. (aacrjournals.org)
  • Importantly, although the side effect hypogammaglobulinemia has been observed with rituximab, the presence of the targeted receptors on both the malignant cells as well as the normal counterparts has not caused significant limitations to these approaches. (aacrjournals.org)
  • Based on molecular profiling breast carcinomas are divided into several subtypes depending on the expression of a number of cell surface receptors, e.g. (nature.com)
  • These drugs target either the homo- or heterodimerization of Her2 receptors or the receptors' RTK activity, both of them being critical for the proliferation of cancer cells. (nature.com)
  • ErbB receptors are localized on the cell membrane surface as inactive monomers. (nature.com)
  • Studies of chemokine receptors (CKR) in natural killer- (NK-) cells have already been published, but only a few gave detailed information on its differential expression on blood NK-cell subsets. (hindawi.com)
  • They comprise, among others, the killer cell immunoglobulin-like receptors (KIR), killer cell lectin type receptors (KLR), and natural cytotoxic receptors (NCR) as well as immunoglobulin Fc receptors (FcR) and complement receptors [ 8 - 10 ]. (hindawi.com)
  • Immunoglobulins and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. (cdc.gov)
  • We hypothesised that the unique properties of IgE, a class of tissue-resident antibodies commonly associated with allergies, which can trigger powerful immune responses through strong affinity for their particular receptors on effector cells, could be employed for passive immunotherapy of solid tumours such as ovarian and breast carcinomas. (springer.com)
  • Examples of monoclonal antibody therapeutics interacting with T cell signaling receptors include Ipilimumab (αCTLA4, or cytotoxic T-lymphocyte 4) as well as Nivolumab and Pembrolizumab (αPD-1, or programmed cell death protein 1). (criver.com)
  • Engagement of receptors on the surface of natural killer (NK) cells initiates a biochemical cascade ultimately triggering cytokine production and cytotoxicity, although the interrelationship between these two outcomes is currently unclear. (rupress.org)
  • In this study we investigate the role of the cell surface phosphatase CD45 in NK cell development and intracellular signaling from activating receptors. (rupress.org)
  • These data, supported by analogous findings after CD16 and NKG2D stimulation of CD45 −/− primary NK cells, place CD45 upstream of SFK in NK cells after stimulation via immunoreceptor tyrosine-based activation motif-containing receptors. (rupress.org)
  • Molecular mechanisms reveal that human cytomegalovirus has evolved to deploy two individual glycoproteins working in synergy to efficiently evade antibody-mediated immunity mediated by Fc-gamma receptors. (elifesciences.org)
  • A family of engineered immune receptors trigger internalization of cancer cells and antigen-coated targets. (elifesciences.org)
  • Retinoid X-receptors (RXRs) are members of the ligand-dependent transcription factor family of nuclear receptors that have gained recent research focus as potential targets for neurodegenerative disor. (bioportfolio.com)
  • In addition to neutralizing antigens, antibodies are also capable of stimulating cellular responses through Fc-Fc receptor interactions. (pnas.org)
  • Antibodies bind to specific antigens on the surface of the target cell (see Fig 1). (tebu-bio.com)
  • The vaccine elicited a variety of antibody responses to both antigens, including neutralizing antibodies and antibodies with antibody-dependent cellular cytotoxic activity specific for GP. (nature.com)
  • Active cellular therapies aim to destroy cancer cells by recognition of distinct markers known as antigens. (wikipedia.org)
  • TG4001 is designed to have a two-pronged antiviral approach: to alert the immune system specifically to HPV-16-infected cells that have started to undergo precancerous transformation (cells presenting the HPV-16 E6 and E7 antigens) and to further stimulate the infection-clearing activity of the immune system through interleukin 2 (IL-2). (biospace.com)
  • Response: Involves production of antibodies and generation of specialized lymphocytes against specific antigens. (scribd.com)
  • The study of reactions between antibodies and antigens. (scribd.com)
  • Humoral (Antibody-Mediated) Immunity (Antibody Involves production of antibodies against foreign antigens. (scribd.com)
  • Cell Mediated Immunity Involves specialized set of lymphocytes called T cells that recognize foreign antigens on the surface of cells. (scribd.com)
  • The most common Fc receptor that exists on the surface of NK Cell is called CD16 or FcγRIII. (bionity.com)
  • Once bound to the Fc receptor of IgG the Natural Killer cell releases cytokines such as IFN-γ, and cytotoxic granules containing perforin and granzymes that enter the target cell and promote cell death by triggering apoptosis . (bionity.com)
  • However, these parasites can become coated with an antibody called IgE that is recognized by an Fc receptor (FcєRI) of eosinophils , a cell type that contains granules (such as major basic protein) against which helminths are not resistant. (bionity.com)
  • The type of response stimulated by these interactions is influenced by both the Fc receptor type expressed on the effector cell and the isotype of antibody to which it is bound. (pnas.org)
  • However, how antibody specificity influences Fc receptor functions, and how antibodies of different specificities interact to modulate these functions, remain unknown. (pnas.org)
  • It has been proposed that antibodies that do not neutralize HIV-1 infection of target cells, as measured in conventional assays, may inhibit viral replication through Fc receptor-mediated effector mechanisms ( 7 , 8 , 12 - 14 ). (asm.org)
  • Interaction between the Fc region of the antibody and the Fc receptor induces the effector cell to degranulate, releasing IFN-γ, granzymes, and other cytotoxic compounds that lyse the target cell. (tebu-bio.com)
  • The system is based on Jurkat cells that stably express human FcγRIIIa (CD16a), the receptor for the Fc region of human IgG. (tebu-bio.com)
  • Mechanisms that may explain these deficits in cord lymphocytes include a decreased ability to translate IL-2 from mRNA ( 46 ) and reduced levels of expression of the γ chain of the IL-2 receptor on the cell membrane ( 30 , 37 , 43 , 44 , 52 ). (asm.org)
  • αβ T-cell receptor bias in disease and therapy (Review). (semanticscholar.org)
  • NK cells expressing an inhibitory KIR-binding self-HLA can be activated when confronted with allografts lacking a ligand for the inhibitory receptor. (escholarship.org)
  • Natural killer cell activation is determined by the balance of inhibitory and activating receptor stimulation. (wikipedia.org)
  • Mononuclear phagocytes, but not NK cells, in both humans and mice also express CD32B (FcγRIIB), an inhibitory Fcγ receptor that functions as a threshold and negative regulator of cell activation ( 7 ). (aacrjournals.org)
  • Further, in SUM190PT cells, therapeutic sensitivity to GW583340 (a dual epidermal growth factor receptor/ErbB2 kinase inhibitor) corresponded with XIAP down-regulation and abrogation of XIAP inhibition on active caspase-9 release. (aacrjournals.org)
  • Once the Fc receptor binds to the Fc region of IgG, the NK cell releases cytotoxic factors that cause the death of the target cell. (wikipedia.org)
  • After washing, effector cells expressing Fc receptor CD16 are co-incubated with the antibody-labelled target cells. (wikipedia.org)
  • NK cells are able to recognize host stress proteins up regulated during viral infections through C type Lectin-like receptor family ( 10 ). (frontiersin.org)
  • The TNF receptor superfamily member CD27 is best known for its important role in T-cell immunity but is also recognized as a cell-surface marker on a number of B- and T-cell malignancies. (aacrjournals.org)
  • Although 1F5 could activate human T cells when combined with T-cell receptor stimulation, 1F5 did not promote the survival or proliferation of freshly isolated lymphoma cells from patients. (aacrjournals.org)
  • Cetuximab is a chimeric mouse-human antibody targeting the extracellular domain of epidermal growth factor receptor (EGFR), and is much-anticipated to improve colorectal cancer therapy. (elsevier.com)
  • However, in cells that had HER2/neu gene amplification and estrogen receptor expression, tamoxifen elevated HER2/neu but failed to improve NK cell function. (aah.org)
  • Molecular basis for antagonistic activity of anifrolumab, an anti-interferon-α receptor 1 antibody. (astrazeneca.com)
  • The HIV accessory protein Nef downregulates the viral entry receptor CD4, the Human Leukocyte Antigen (HLA)-A and -B molecules, the Serine incorporator 5 (SERINC5) protein and other molecules from the infected cell surface, thereby promoting viral infectivity, replication and immune evasion. (springer.com)
  • Our laboratory has examined this concept by evaluating two chimaeric antibodies of the same specificity (MOv18) but different isotype, an IgG1 and an IgE against the tumour antigen folate receptor α (FRα). (springer.com)
  • Type-I interferon enriched microenvironment generated by Mycobacterium tuberculosis induces the Siglec-1 receptor expression in human macrophages, including on tunneling nanotubes, and contributes to the exacerbation of cell-to-cell transfer of HIV-1. (elifesciences.org)
  • A receptor for antibody on B lymphocytes. (springer.com)
  • Stimulation via the major histocompatibility complex I-binding receptor, Ly49D on CD45 −/− primary NK cells resulted in the activation of phosphoinositide-3-kinase and normal cytotoxicity but failed to elicit a range of cytokines and chemokines. (rupress.org)
  • Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. (astrazeneca.com)
  • The present invention provides agents comprising or consisting of a binding moiety with specificity for interleukin-1 receptor accessory protein (IL1RAP) for use in inducing cell death and/or inhibiting the growth and/or proliferation of cells associated with a solid tumour, wherein the cells express IL1RAP. (freepatentsonline.com)
  • A related aspect of the invention provides agents comprising or consisting of a binding moiety with specificity for interleukin-1 receptor accessory protein (IL1RAP) for use in detecting pathological cells associated with a solid tumour, wherein the cells express IL1RAP. (freepatentsonline.com)
  • Nitric Oxide Production by Myeloid Derived Suppressor Cells Plays a Role in Impairing Fc Receptor-Mediated Natural Killer Cell Function. (osu.edu)
  • In NK cells, the presence of a γ/ζ heterodimer or of a ζ/ζ homodimer has also been reported (the ζ chain is also part of the T cell receptor ( TcR ) complex). (els.net)
  • In addition, we show that interactions among antibodies that bind to discrete epitopes on the same antigen can influence the induction of Fc-dependent effector functions. (pnas.org)
  • Class of specific cytotoxic cells demonstrated in vitro by arming with antigen‐antibody complexes. (currentprotocols.com)
  • IgG1 binding to NK cells was increased by ligating IgG1 with clustered antigen, especially for low-fucose IgG1. (aacrjournals.org)
  • Usually, a target cell line expressing a certain surface-exposed antigen is incubated with antibody specific for that antigen. (wikipedia.org)
  • This appears to reflect a ceiling at which increasing antigen expression fails to improve NK cell effector function. (aah.org)
  • This has clinical implications as trying to increase antigen expression to enhance NK cell function may be useful for patients with antigen-low tumors, but not in those whose tumors have gene amplification or high levels of antigen expression. (aah.org)
  • Comparative analysis of activation induced marker (AIM) assays for sensitive identification of antigen-specific CD4 T cells. (chavi-id.org)
  • 3. IL-2 secreted by Th1 or Th17 CD4+ cell or the CTL itself result in the proliferation and differentiation of the antigen-activated CTL-P cell to fully active CTL. (brainscape.com)
  • Dendritic cells are antigen presenting cells (APCs) in the mammalian immune system. (wikipedia.org)
  • An anti-CD52 ANTIGEN monoclonal antibody used for the treatment of certain types of CD52-positive lymphomas (e.g. (bioportfolio.com)
  • IntroductionThe cutaneous lymphocyte antigen interacts with E-selectin on endothelial cells and is expressed on 15% of circulating T-cells. (bioportfolio.com)
  • Skin-homing T-cells express the cutaneous lymphocyte antigen. (bioportfolio.com)
  • Nitric oxide mediated inhibition of antigen presentation from DCs to CD4(+) T cells in cancer and measurement of STAT1 nitration. (osu.edu)
  • The CD40 molecule is mainly expressed on antigen-presenting cells such as macrophages, and dendritic cells (DCs) as well as on B lymphocytes and appears to play an important role in immunological responses 1 . (pubmedcentralcanada.ca)
  • Serum containing antibodies to a specific antigen(s). (scribd.com)
  • Immune Reconstitution Following Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma at the Time of Immunotherapy. (semanticscholar.org)
  • The recent FDA approvals of immune checkpoint inhibitor monoclonal antibodies (mAb) constitute a major advance in the immunotherapy of cancer. (aacrjournals.org)
  • Weiner LM, Surana R, Wang S (2010) Monoclonal antibodies: versatile platforms for cancer immunotherapy. (springer.com)
  • It is one of the mechanisms through which antibodies, as part of the humoral immune response , can act to limit and contain infection. (bionity.com)
  • 1F5 significantly enhanced the survival of SCID mice bearing Raji or Daudi tumors, which may be mediated through direct effector mechanisms such as antibody-dependent cellular cytotoxicity. (aacrjournals.org)
  • The treatment of chronic lymphocytic leukaemia (CLL) has been improved by introduction of monoclonal antibodies (mAbs) that exert their effect through secondary effector mechanisms. (forskningsdatabasen.dk)
  • We investigated the possible positive or negative impact of these drugs on all known mechanisms of action of both type I and type II anti-CD20 antibodies. (haematologica.org)
  • In contrast, ibrutinib strongly inhibited all cell-mediated mechanisms induced by anti-CD20 antibodies rituximab, ofatumumab or obinutuzumab, either in purified systems or whole blood assays. (haematologica.org)
  • Finally we show that the phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib similarly inhibited the immune cell-mediated mechanisms induced by anti-CD20 antibodies, although the effects of this drug at 10 μM were weaker than those observed with ibrutinib at the same concentration. (haematologica.org)
  • We also applied this notion to a marketed therapeutic, the humanised IgG1 antibody trastuzumab and engineered an IgE counterpart, which retained the functions of trastuzumab in restricting proliferation of HER2/ neu -expressing tumour cells but also activated effector cells to kill tumour cells by different mechanisms. (springer.com)
  • As described for MDS, both innate and adaptive immunities are eluded by AML blasts through different mechanisms: (1) suppression of NK cell-mediated cytotoxicity by the inability to lyse AML cells, production of cytotoxic cytokines, aberrant expression of VEGFC, and by immature NK cell inhibition of T cell activation. (thefreedictionary.com)
  • Laboratory work has centered on the mechanisms of how cells acquire specific fates during growth and development, providing insights into normal and abnormal mechanisms of growth control. (stanford.edu)
  • Natural killer (NK) cells of the innate immune system are cytotoxic lymphocytes that play an important roles following transplantation of solid organs and hematopoietic stem cells. (escholarship.org)
  • Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic cells to promote cellular and humoral adaptive immune responses against the allograft. (escholarship.org)
  • Natural killer cells, or NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system . (wikipedia.org)
  • The role NK cells play is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response . (wikipedia.org)
  • Typically, immune cells detect major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing lysis or apoptosis . (wikipedia.org)
  • NK cells are unique, however, as they have the ability to recognize stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. (wikipedia.org)
  • [1] This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells. (wikipedia.org)
  • [7] The role of NK cells in both the innate and adaptive immune responses is becoming increasingly important in research using NK cell activity as a potential cancer therapy. (wikipedia.org)
  • In the early phases of cancer immune surveillance, NK cells directly identify and lyse cancer cells. (frontiersin.org)
  • However, a class of important immune-modulators is conspicuously absent: agents that utilize the power of innate immune cells to eradicate tumors. (frontiersin.org)
  • An important class of innate immune cells that play a critical role in mediating the antitumor immune response is the natural killer (NK) cell. (frontiersin.org)
  • NK cells play a key role in immune response against HIV infection. (frontiersin.org)
  • These cells can destroy infected cells and contribute to adequate and strong adaptive immune responses, by acting on dendritic, T, B, and even epithelial cells. (frontiersin.org)
  • NK cells are also involved in regulatory functions, by improving CD8 + T cell responses against viral infection ( 15 ), inhibiting the size/functionality of the T cell response and regulating crosstalk network with dendritic cells (DCs) and neutrophils to promote or hamper the immune response ( 16 , 17 ). (frontiersin.org)
  • Antibodies engage the immune system with their Fc, stimulating immune cell effector function. (aah.org)
  • Moreover, our results suggest that HIV-1 CD4 downregulation might help avoid the killing of HIV-1-infected cells by this immune mechanism. (duke.edu)
  • Natural killer- (NK-) cells were originally identified by their natural ability to kill target cells and are known for a long time as effector cells of the innate immune system, with an important role in controlling several types of tumors and infections [ 1 ]. (hindawi.com)
  • In recent years, NK-cells have also been recognized as regulatory cells, which are able to interact with other cells of the immune system, such as dendritic cells (DC), monocytes/macrophages, and T cells, thereby influencing the innate and adaptive immune responses [ 2 - 5 ]. (hindawi.com)
  • Meanwhile, the immunoregulatory properties of the NK-cells are mediated, not only by cell-to-cell contact, but also by the soluble factors they produce, which enable them to recruit and to activate other immune cells. (hindawi.com)
  • In addition, drugs that inhibit the immune checkpoints programmed cell death protein 1 (PD-1) and its major ligand, programmed death-ligand 1 (PD-L1), have shown clinical activity in diverse cancer types [ 9 - 11 ]. (oncotarget.com)
  • Binding between programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) provides immune evasion through which cancer can escape a host immune response. (bmj.com)
  • Recent studies have revealed the molecular pathways that preserve the viability of senescent cells and the ones regulating their immune surveillance. (jci.org)
  • B ) The second type of strategy is to potentiate an immune response against senescent cells in a way that would lead to their clearance from tissues. (jci.org)
  • The purpose of this Funding Opportunity Announcement (FOA) is to support multidisciplinary, hypothesis-driven research on Natural Killer (NK) cells, leading to the discovery of pathways relevant for early immune responses and immune regulation impacting the potential protective immunity to be induced by HIV vaccination. (nih.gov)
  • This Funding Opportunity Announcement (FOA) invites applications to study the immunomodulatory or effector roles of Natural Killer (NK) cells in facilitating and/or regulating the antiviral adaptive immune responses in the context of HIV-1 vaccines. (nih.gov)
  • The outcome of these research projects should provide novel approaches to harness NK cell immunoregulatory functions in HIV-1 vaccine design and also to enhance protective HIV-1 specific adaptive immune responses. (nih.gov)
  • Finally, specific antibodies can be developed that recognize cancer cells and target them for destruction by the immune system. (wikipedia.org)
  • Passive antibody therapies aim to increase the activity of the immune system without specifically targeting cancer cells. (wikipedia.org)
  • This enhances the ability of the immune system to attack cancer cells. (wikipedia.org)
  • Monoclonal antibody therapeutics targeting immune checkpoint inhibitors or activators are a heterogeneous class of T cell modulating drug. (criver.com)
  • Along with our assay experience, Charles River is also able to help support our clients' regulatory questions and make sure that their program meets guidelines specifically aimed at immune checkpoint antibodies. (criver.com)
  • The activation of NK cells forms part of the innate immune response to parasites, tumors, and virally infected cells and is important for their clearance ( 1 ). (rupress.org)
  • SOTIO's robust clinical pipeline includes a differentiated superagonist of the attractive immuno-oncology target IL-15, a platform to streamline personalized active immune cell therapies and a new generation of potent and stable antibody-drug conjugates (ADCs). (b3cnewswire.com)
  • Moreover, with a deepening understanding, emerging evidence has shown that immune dysfunctions caused by HT conditions, including imbalanced subsets of CD4+ T-helper cells, B regulatory (Breg) cells, high expression levels of CD56dim natural killer (NK) cells, and cytokines, possibly play an important role in impairing maternal tolerance to the fetus. (medsci.org)
  • In recent years, unprecedented progress has been made in recognizing the specific changes in immune cells and molecules in patients with HT, which will be helpful in exploring the mechanism of HT-related miscarriage. (medsci.org)
  • defence against bacteria.Duality of Immune System I. . antibodies and are called plasma cells. (scribd.com)
  • or tissues: Helper T cells Cytotoxic T cells T cells regulate proliferation and activity of other cells of the immune system: B cells. (scribd.com)
  • Similarly, antibody-coated HRBC targets in suspension could be lysed normally by CGD effector cells when phagocytosis was inhibited by the addition of in vitro colchicine. (nih.gov)
  • MEDI-563 potently induces antibody-dependent cell-mediated cytotoxicity of both eosinophils (half-maximal effective concentration = 0.9 pmol/L) and basophils (half-maximal effective concentration = 0.5 pmol/L) in vitro. (garvan.org.au)
  • The high expression of CD27, a T-cell costimulatory molecule, on many types of lymphoma and leukemia prompted us to develop human anti-CD27 mAbs and determine their activity against lymphoma cells in vitro and in vivo . (aacrjournals.org)
  • In vitro ASKP1240 concentration-dependently inhibited human peripheral blood mononuclear cell proliferation induced by soluble CD154. (pubmedcentralcanada.ca)
  • Using influenza A virus as a model, we demonstrate that antibody specificity profoundly influences the induction of antibody-dependent cell-mediated cytotoxicity by effector cells. (pnas.org)
  • There was no single anti-HIV-1 antibody specificity that was a clear correlate of immunity in controllers. (ovid.com)
  • Improving target cell specificity using a novel monovalent bispecific IgG design. (astrazeneca.com)
  • Development and validation of an antibody-dependent cell-mediated cytotoxicity-reporter gene assay. (nih.gov)
  • The levels of these different antibody responses and HIV-specific CD8 T cell responses quantified by enzyme-linked immunosorbent spot (ELISPOT) IFNγ assay were compared in each controller. (ovid.com)
  • The most common method for measuring cell-mediated cytotoxicity is the release assay. (biomedcentral.com)
  • Waters-Peacocke, N , Wray, BB & Ades, EW 1988, ' A prospective study: Evaluation of the antibody-dependent cell-mediated cytotoxicity assay in Chronic active Epstein-Barr syndrome ', Journal of Clinical and Laboratory Immunology , vol. 27, no. 1, pp. 11-12. (elsevier.com)
  • NK cell cytotoxicity was measured by 51 Cr-release assay and CD107a degranulation assay. (bmj.com)
  • A plaque technique for assay and characterization of antibody-dependent cytotoxic effector (K) cells. (springer.com)
  • Role of anaphylactic antibodies in immunity to schistosomes. (currentprotocols.com)
  • It is now well established that target cell destruction can be mediated through the interaction of antibody with normal lymphoid cells as well as through the classic T-cell immunity mechanism ( Cerottini and Brunner , 1974). (springer.com)
  • Red blood cells infected by the malaria parasite Plasmodium falciparum are destroyed by human natural killer cells in the presence of antibodies from people who have acquired clinical immunity to malaria. (elifesciences.org)
  • Naturally Acquired Passive Immunity: Immunity: Antibodies pass from mother to fetus via placenta or breast feeding (colostrum). (scribd.com)
  • 2. . Artificially Acquired Passive Immunity: Immunity: Preformed antibodies (antiserum) are introduced into body antiserum) by injection. (scribd.com)
  • Augmentation of antibody dependent cell mediated cytotoxicity following in vivo therapy with recombinant interleukin 2. (semanticscholar.org)
  • Analysis of anti-CD20 mediated activation of natural killer cells isolated from patients on continued oral ibrutinib treatment suggested that repeated drug dosing inhibits these cells in vivo . (haematologica.org)
  • Because of the broad neutralization and in vivo protection across influenza A and influenza B virus strains, monoclonal antibody CR9114 is widely used in influenza virus research as a positive control in many experiments. (pubmedcentralcanada.ca)
  • Unexpectedly, in experiments mimicking adjuvant therapy of submacroscopic disease in vivo (JIMT-1 cells inoculated s.c. in severe combined immunodeficiency mice), trastuzumab was able to inhibit the outgrowth of macroscopically detectable xenograft tumors for up to 5-7 weeks. (aacrjournals.org)
  • An in-depth view of the in vivo blood and tissue HIV reservoir is presented highlighting shared phenotypic features between individuals, thus enabling marked ex vivo enrichment of replication-competent latent cells. (elifesciences.org)
  • Strategies to augment the antitumor response by NK cells have led to an increased understanding of how to improve their effector responses. (hindawi.com)
  • This is similar to, but independent of, responses by cytotoxic T cells (CTLs). (bionity.com)
  • however, the kinetics of the measured responses were the same using these different target cells. (asm.org)
  • The findings of the recently reported human immunodeficiency virus type 1 (HIV-1) vaccine trial in Thailand (RV144) have refocused interest on vaccine-elicited antibody responses. (asm.org)
  • Since this vaccine regimen elicited nonneutralizing antibody and CD4 + T cell responses, attention is turning to the possibility that nonneutralizing antibodies may have mediated the protection seen in this clinical trial. (asm.org)
  • Regardless of the type of antibody tested, there was no correlation with HIV-specific CD8 T cell responses. (ovid.com)
  • Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity. (chavi-id.org)
  • found that trastuzumab-F(ab′) 2 and a mixture of F(ab′) 2 fragments of three anti-ErbB2 immunoglobulin G (IgG) exerted significantly reduced responses compared with those of trastuzumab IgG and the mixture of the three anti-ErbB2 IgGs in mice xenografted with trastuzumab-sensitive breast cancer cells ( 17 ). (aacrjournals.org)
  • Thus we identify CD45 as a pivotal enzyme in eliciting a precise subset of NK cell responses. (rupress.org)
  • 19 ). The association of NKG2D with at least two distinct adaptor proteins suggests it may activate distinct signal pathways that may result in distinct cellular responses such cytokine/chemokine production versus cytotoxicity. (rupress.org)
  • Thus recruitment of either DAP12 or DAP10 appears to activate independent biochemical pathways leading to distinct cellular responses, although this has yet to be confirmed in primary cells. (rupress.org)
  • By using mice transgenic for human CD16A , enhanced survival was observed due to expression of CD16A-158 phe on monocytes and macrophages as well as on NK cells in these mice. (aacrjournals.org)
  • Activation of natural killer cells, and antibody-dependent cellular cytotoxicity by these cells, as well as phagocytosis by macrophages or neutrophils were inhibited by ibrutinib with a half maximal effective concentration of 0.3-3 μM. (haematologica.org)
  • Efforts at using NK cells as antitumor agents began over two decades ago, but recent advances in elucidating NK cell biology have accelerated the development of NK cell-targeting therapeutics. (frontiersin.org)
  • Severe combined immunodeficient (SCID) mice inoculated with human CD27-expressing lymphoma cells were administered 1F5 to investigate direct antitumor effects. (aacrjournals.org)
  • Background Although programmed cell death-1/programmed death-ligand 1 (PD-L1) inhibitors show remarkable antitumor activity, a large portion of patients with cancer, even those with high PD-L1-expressing tumors, do not respond to their effects. (bmj.com)
  • This crosslinking causes the Jurkat cells to activate NFAT transcription, which induces the expression of luciferase and can be easily detected using the ONE-Step™ Luciferase Detection Reagents . (tebu-bio.com)
  • The G1/S checkpoint process selectively induces cell cycle arrest in cancer cells with irreparable DNA damages and triggers subsequent apoptosis, while allowing cell division to proceed in cells without or with minor reparable DNA damage. (cancer.gov)
  • This study implicates the response to rituximab in NHL patients to cells that express CD32A, a subgroup of leukocytes that includes neutrophils and mononuclear phagocytes, but not NK cells. (aacrjournals.org)
  • Since the initial approval of rituximab in 1997, the continued success of monoclonal antibody (mAb) therapy in treating various types of lymphoma and leukemia has spurred considerable development of novel therapeutics, including both naked antibody approaches and antibody-drug conjugates ( 1, 2 ). (aacrjournals.org)
  • Importantly, an anti-CD5 mAb combination enhanced CDC of CLL cells when combined with the anti-CD20 mAbs rituximab and ofatumumab as well as with the anti-CD52 mAb alemtuzumab. (forskningsdatabasen.dk)
  • The anti-CD20 antibody rituximab is approved for the treatment of B-cell non-Hodgkin lymphoma (B-NHL) and chronic lymphocytic leukemia (CLL) in combination with chemotherapy. (haematologica.org)
  • Examples of such antibodies include rituximab (targeting CD-20), trastuzumab (targeting HER-2), and cetuximab (targeting EGFR). (wikipedia.org)
  • By comparing NK cell expression of CD107a with NK cell expression of other cytokines or chemokine molecules, we found that measuring CD107a expression is sufficient for evaluating the anti-SIV function of NK cells. (asm.org)
  • Incubation with IL-2 (100 U/ml) or IL-12 (1 ng/ml) for 18 h increased the NK cell activity (using K562 target cells) of both cord blood and adult MNCs, and the combination of IL-2 and IL-12 increased cord blood cytotoxicity threefold, making the cytotoxicity of cord blood cells equivalent to that of adult cells treated with the same cytokines. (asm.org)
  • Previous studies have demonstrated that MNCs from newborn infants have a reduced capacity to produce cytokines, particularly interleukin-2 (IL-2) and gamma interferon (IFN-γ) ( 1 , 6 , 22 , 27 , 48 ), both of which are important in upregulating the cytotoxicity of NK cells ( 4 , 5 , 45 ). (asm.org)
  • Cytokines, cancer vaccines, adoptive cell transfers, and especially checkpoint inhibitors constitute valuable elements in the immunotherapeutic armamentarium. (frontiersin.org)
  • The cytokines released from activated T cells accumulate inflammatory cells in the region, and this leads to cell-mediated cytotoxicity and keratinocyte destruction. (thefreedictionary.com)
  • Upon topical application of the East Indian sandalwood oil (EISO) cream to an affected area of skin, the active ingredients in the cream may suppress various enzymes, such as cyclooxygenase (COX) and cyclic adenosine monophosphate (cAMP) phosphodiesterases (PDEs), prevent the production of pro-inflammatory cytokines and chemokines and directly cause apoptosis in susceptible cell types, including certain cancer cells and virally-infected cells. (cancer.gov)
  • More than half of all biotherapeutics are glycosylated (2), including monoclonal antibodies (mAbs), Fc-fusion proteins, clotting factors, and cytokines such as erythropoietin. (biopharminternational.com)
  • In the presence of a 1/6.25 × 10 6 dilution of antichicken erythrocyte rabbit IgG, cell lysis increased from 20% to 65% by the attachment of 18,000 C3b molecules per cell. (jimmunol.org)
  • Extracellular lysis of autologous antibody-coated lymphoid cell targets in suspension was mediated normally by CGD effector cells. (nih.gov)
  • The three components are mixed in microtiter‐plate wells and lysis of the target cells is detected by measuring the release of radioactivity into the cell supernatant. (currentprotocols.com)
  • Over the course of a few hours a complex forms between the antibody, target cell, and effector cell which leads to lysis of the cell membrane of the target. (wikipedia.org)
  • If the target cell was pre-loaded with a label of some sort, that label is released in proportion to the amount of cell lysis. (wikipedia.org)
  • Target cell lysis is determined by measuring the amount of radiolabel released into the cell culture medium by means of a gamma counter or scintillation counter. (wikipedia.org)
  • An immunologic response in which an immunologic effector cell binds to a target cell coated with antibodies, triggering a series of metabolic events that leads to lysis of the target cell. (thefreedictionary.com)
  • Heteroantibody- versus conventional antibody-mediated target cell lysis. (rochester.edu)
  • Indeed, NK cells lacking Lck ( 23 ) and Fyn ( 23 , 24 ) appear grossly normal, although a role for Fyn in the lysis of cells lacking MHC-I and NKG2D ligands has been reported ( 25 ). (rupress.org)
  • This binding initiates secretion of granzyme and perforin by NK cells resulting in the lysis of the target cell [ 7 ]. (biomedcentral.com)
  • The need for biologically relevant assays with clinical translatability has brought the 3D cell culture model to the forefront of drug discovery. (selectscience.net)
  • In this application note, the suitability of Kuraray's Elplasia Square Type plates for antibody-dependent cell mediated cytotoxicity assays, using 3D cell culture, is tested. (selectscience.net)
  • Such long-lasting molecules have the potential to make an impact in the field of antibody-based therapy. (astrazeneca.com)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • Although the targets of these molecules are different, the goal is the same: modulate T cell reactivity to tumors by blocking inhibitory pathways or enhancing stimulatory pathways. (criver.com)
  • Effector cells are then activated and release molecules that will lead to the death of tumour cells. (els.net)
  • This antibody is first detected in mice with regressing tumors. (jimmunol.org)
  • Functional properties and effect on growth suppression of human neuroblastoma tumors by isotype switch variants of monoclonal antiganglioside GD2 antibody 14.18. (semanticscholar.org)
  • There is compelling clinical and experimental evidence to suggest that natural killer (NK) cells play a critical role in the recognition and eradication of tumors. (frontiersin.org)
  • Natural killer (NK) cells play a key role in the host defense given their cytotoxic activity against tumors and virus-infected cells ( 1 ). (frontiersin.org)
  • Besides down regulation of HLA, NK cells can recognize several MHC-related ligands that are up-regulated on various tumors ( 12 ), including UL16-binding proteins (ULBP1-6) and MHC class I-chain-related proteins A and B (MICA and MICB) ( 13 , 14 ). (frontiersin.org)
  • Several FDA-approved drugs for the treatment of Her2-positive tumors have been developed, although eventually cancer cells develop drug resistance. (nature.com)
  • Because cancer cell growth is often driven by highly overexpressed oncogenes, even late-stage tumors can be successfully treated with therapies directed against the overexpressed oncoprotein ( 5 , 6 ). (aacrjournals.org)
  • This variation results in human IgG1 antibodies binding with higher affinity to the NK cells of homozygous FCGR3A -158V donors than those of homozygous FCGR3A -158F donors, and seems to result in more effective NK cell activation (8, 9) . (aacrjournals.org)
  • Girentuximab (trade name Rencarex) is a chimeric IgG1 monoclonal antibody to carbonic anhydrase IX (CAIX). (wikipedia.org)
  • Avelumab is a human anti-PD-L1 IgG1 monoclonal antibody. (biospace.com)
  • Humanized monoclonal antibodies (mAbs) are the fastest growing class of biological therapeutics that are being developed for various medical indications, and more than 30 mAbs are already approved and in the market place. (nih.gov)
  • On-going efficacy, safety evaluations and future first-in-man clinical studies of IgE therapeutics constitute key metrics for this concept, providing new scope for antibody immunotherapies for solid tumours. (springer.com)
  • Li J, Zhu Z (2010) Research and development of next generation of antibody-based therapeutics. (springer.com)
  • At the same time they stress the need to understand the limitations of the existing strategies, their efficacy and safety, and the possible deleterious consequences of senescent cell elimination. (jci.org)
  • Induction of HL60 cell differentiation by tiazofurin and its analogues: characterization and efficacy. (rochester.edu)
  • Its development was suspended as a "naked" or unconjugated antibody during phase III trials due to efficacy. (wikipedia.org)
  • The influence of N-glycans on the efficacy, stability, half-life, and safety of antibody and antibody-derived biotherapeutics are well-reviewed (5, 13, 14) and are summarized in Figure 1 . (biopharminternational.com)
  • With the recent demonstration in the RV144 Thai trial that a vaccine regimen that does not elicit neutralizing antibodies or cytotoxic T lymphocytes may confer protection against human immunodeficiency virus type 1 (HIV-1) infection, attention has turned to nonneutralizing antibodies as a possible mechanism of vaccine protection. (asm.org)
  • Increased NK cell activity reflected by higher cytotoxic capacity, IFN-γ and chemokines (CCL3, CCL4, and CCL5) production, has been associated with resistance to HIV infection and delayed AIDS progression, demonstrating the importance of these cells in the antiviral response. (frontiersin.org)
  • Recently, a subpopulation of NK cells with adaptive characteristics has been described and associated with lower HIV viremia and control of infection. (frontiersin.org)
  • in addition, changes including phenotypic, functional and frequency modifications during HIV infection will be pointed, highlighting opportunities to vaccine development based in NK cells effector functions. (frontiersin.org)
  • The Early Antibody-Dependent Cell-Mediated Cytotoxicity Response Is Associated With Lower Viral Set Point in Individuals With Primary HIV Infection. (ox.ac.uk)
  • A subset of EC/VCs have CD4+T cells with resistance specific to R5-tropic HIV infection associated with transcriptional down-regulation of ccr5 , a phenotype that appears to be heritable, across multiple generations. (elifesciences.org)
  • For example, recognition of H-2d ( 2 ) or murine cytomegalovirus (MCMV) encoded m157 ( 3 ) by Ly49D and Ly49H respectively, results in cell-mediated cytotoxicity and large scale production of IFN-γ and, in response to MCMV infection, chemokines such as MIP-1α, MIP-1β, RANTES, and ATAC ( 4 - 7 ). (rupress.org)
  • Cigarette smoke silences innate lymphoid cell function in the lung, facilitating an interleukin-33-dependent, exacerbated type I response to infection. (astrazeneca.com)
  • Molluscum contagiosum infection with features of primary cutaneous anaplastic large cell lymphoma. (bioportfolio.com)
  • NK cells (belonging to the group of innate lymphoid cells ) are defined as large granular lymphocytes (LGL) and constitute the third kind of cells differentiated from the common lymphoid progenitor -generating B and T lymphocytes . (wikipedia.org)
  • Antibodies are produced by a subset of lymphocytes called B cells. (scribd.com)
  • B) Anti-CD20 isotype antibody induced NFAT driven luciferase activity in Jurkat cells expressing human FcγRIIIa. (nih.gov)
  • Consistent with this clinical observation, B-cell depletion in mice treated with an anti-CD20 mAb was independent of NK cells, but proceeded via an FcγR-dependent mechanism that required mononuclear phagocytes ( 5 ). (aacrjournals.org)
  • CLL cells are characterized by expression of CD5 and CD23 along with CD19 and CD20, hence anti-CD5 Abs that engage secondary effector functions represent an attractive opportunity for CLL treatment. (forskningsdatabasen.dk)
  • The novel Bruton tyrosine kinase inhibitor ibrutinib and phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib are promising drugs for the treatment of chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma, either alone or in combination with anti-CD20 antibodies. (haematologica.org)
  • Pretreatment with ibrutinib for 1 hour did not increase direct cell death of cell lines or chronic lymphocytic leukemia samples mediated by anti-CD20 antibodies. (haematologica.org)
  • We conclude that the design of combined treatment schedules of anti-CD20 antibodies with these kinase inhibitors should consider the multiple negative interactions between these two classes of drugs. (haematologica.org)
  • The next generation anti-CD20 monoclonal antibodies, ofatumumab 1 and obinutuzumab (GA101), 2 were approved more recently and are in clinical trials for the treatment of CLL and B-NHL, combined with either standard or novel chemotherapeutic agents. (haematologica.org)
  • Ofatumumab acts by complement-dependent and antibody-dependent cell-mediated cytotoxicity by binding to a small different epitope of CD20, and is currently an approved intravenous drug for use in chronic lymphocytic leukemia (3). (thefreedictionary.com)
  • It enables facile quantification of cell-mediated cytotoxicity and evaluation of the potencies of specific antibodies. (biomedcentral.com)
  • HIV-specific antibodies that mediate antibody-dependent cellular cytotoxicity vary in their paths to achieve function but commonly rely on mutations in multiple regions, including framework regions, to reach full potency. (elifesciences.org)
  • Cell types that can be used in this way are natural killer (NK) cells, lymphokine-activated killer cells, cytotoxic T cells and dendritic cells. (wikipedia.org)
  • It may be a Lymphocyte lacking conventional B- or T-Cell markers, or a Monocyte , Macrophage , or polynuclear Leukocyte , depending on the identity of the target Cell . (online-medical-dictionary.org)
  • NK Cells are not a subset of the T lymphocyte family. (wikipedia.org)
  • Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. (cdc.gov)
  • Lymphocyte cytotoxicity induced by preincubation with serum from patients with Hashimoto thyroiditis. (springer.com)
  • Extracellular killing of sensitized targets does not appear to be dependent upon the generation of hydrogen peroxide (H2O2) ANd/or superoxide (02-) and is normal in CGD neutrophils and monocytes. (nih.gov)
  • The binding of an IgG antitumour mAb to the target cell (here a tumour cell) allows the recruitment and crosslinking of activating FcγR expressed by effector cells ( NK cells, neutrophils, etc. (els.net)
  • NK-92-CD16 (CD16-transduced NK-92 cell line) and peripheral blood mononuclear cells from healthy donors, respectively, were used as an effector cell. (bmj.com)
  • We investigated associations of total circulating IgG and peripheral blood mononuclear cells glycosylation with AITD and the influence of genetic background in a case-control study with several independent cohorts and over 3,000 individuals in total. (cdc.gov)
  • The study revealed an inverse association of IgG core fucosylation with TPOAb and AITD, as well as decreased peripheral blood mononuclear cells antennary α1,2 fucosylation in AITD, but no shared genetic variance between AITD and glycosylation. (cdc.gov)
  • Tyrosine kinase inhibitors as modulators of trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity in breast cancer cell lines," Cellular Immunology, vol. (thefreedictionary.com)
  • Wick, "Endothelial cell apoptosis in systemic sclerosis is induced by antibody-dependent cell-mediated cytotoxicity via CD95," Arthritis & Rheumatism, vol. (thefreedictionary.com)
  • A ) The leading options are strategies that induce apoptosis selectively in senescent cells with the use of senolytic drugs, which block prosurvival pathways. (jci.org)
  • In addition, like other members of the class, Debio 1143 promotes apoptosis of cancer cells by mimicking the activity of the natural Second Mitochondrial-derived Activator of Caspases (SMAC). (newswire.ca)
  • Although the precise mechanism of TCMR is still unclear, cell-mediated cytotoxicity of parenchymal cells and local cytokine release are two possible causes [6]. (thefreedictionary.com)
  • Bexarotene protects against neurotoxicity partially through a PPARγ-dependent mechanism in mice following traumatic brain injury. (bioportfolio.com)
  • Here, we report the development of a serum-free CHO DG44 cell line, stably producing a CR9114-like antibody with a potential to become a useful influenza virus research tool. (pubmedcentralcanada.ca)
  • Additionally, many (commonly available) cell lines used for transient transfection are serum-dependent, resulting in contamination of produced mAbs by bovine IgGs. (pubmedcentralcanada.ca)
  • Here, we decided to take advantage of a biotechnology-relevant production cell line, Chinese hamster ovary (CHO) DG44, to establish a serum-free, stable, CR9114-like (CR9114L, a generic version of CR9114) antibody-producing cell line for a steady supply of this mAb with low batch to batch variation. (pubmedcentralcanada.ca)
  • Loss of specific natural cell-mediated cytotoxicity with absorption of natural antibodies from serum. (springer.com)
  • Antiserum: Antiserum: Serology: Serology: Gamma Globulins: Globulins: Fraction of serum that contains most of the antibodies. (scribd.com)
  • Serum: Serum: Fluid that remains after blood has clotted and cells have been removed. (scribd.com)
  • And ASKP1240 itself did not activate platelet and endothelial cells. (pubmedcentralcanada.ca)
  • E7820 inhibits angiogenesis by suppressing integrin alpha 2, a cell adhesion molecule expressed on endothelial cells. (cancer.gov)
  • The levels of antibody against the gp120 CD4 binding site, gp41, as well as Env epitopes near to the sites bound by broadly nAbs 2F5 and 1b12 were not different between HICs and viremic individuals. (ovid.com)
  • Antibodies can then bind to these viral proteins. (wikipedia.org)
  • The diagram represents a NK cell containing granules that polarised towards the contact zone with tumour cell once FcγRIIIa (CD16) has been engaged and crosslinked. (els.net)
  • Enhancement of antibody-dependent cytotoxicity with a chimeric anti-GD2 antibody. (semanticscholar.org)
  • However, many therapeutic antibodies currently approved or under clinical development are produced using Chinese hamster ovary cells that express high level of α1,6-fucosyltransferase and consequently produce low amounts antibody lacking fucose (17) . (aacrjournals.org)
  • Therapeutic antibodies have revolutionised treatment of some cancers and improved prognosis for many patients. (springer.com)
  • Dimitrov DS, Marks JD (2009) Therapeutic antibodies: current state and future trends-is a paradigm change coming soon? (springer.com)
  • Product quality attributes are critical for the functionality and manufacturability of therapeutic antibodies. (bioprocessintl.com)
  • Background Seasonal influenza vaccines aim to induce strain-specific neutralizing antibodies. (cdc.gov)
  • The finding that some of the anti-ErbB2 antibodies can inhibit the growth of cancer cells overexpressing ErbB2 on their surface was a breakthrough in anticancer therapy ( 7 ) and led to the development of trastuzumab (Herceptin), a recombinant humanized monoclonal antibody against the extracellular domain of ErbB2. (aacrjournals.org)
  • Primary human eosinophils and basophils were used to demonstrate antibody-dependent cell-mediated cytotoxicity. (garvan.org.au)
  • Human NK cells are phenotypically characterized by the expression of CD56 and the absence of CD3 and can be further subdivided into a CD56 bright population and a CD56 dim population. (frontiersin.org)
  • In this article, we describe a novel human monoclonal antibody (mAb) specific for CD27 with properties that suggest a potential utility against malignancies that express CD27. (aacrjournals.org)
  • The anti-CD27 mAb 1F5 was effective in mediating antibody-dependent cellular cytotoxicity of human lymphoblastic cell lines and significantly reduced their growth when transplanted into immunodeficient mice. (aacrjournals.org)
  • Structural Insights into the Neutralization Properties of the Fully Human, Anti-interferon Monoclonal Antibody Sifalimumab. (astrazeneca.com)
  • Patients without progressive disease (PD) or elevated human antimouse antibody titers could be treated again beginning 3 weeks after completion of a cycle. (mendeley.com)
  • Clinically available antibodies belong to the IgG class, the most prevalent antibody class in human blood, while other classes have not been extensively considered. (springer.com)
  • Bruggemann M, Williams GT, Bindon CI, Clark MR, Walker MR, Jefferis R, Waldmann H, Neuberger MS (1987) Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. (springer.com)
  • in 2012 in a study describing broadly neutralizing human antibodies against influenza B virus strains [ 1 ]. (pubmedcentralcanada.ca)
  • Human alveolar macrophage FcR-mediated cytotoxicity. (rochester.edu)
  • Characterization of human lymphoid cell-mediated antibody-dependent cytotoxicity (LDAC). (springer.com)
  • Avelumab is a human programmed death ligand-1 (PD-L1) blocking antibody. (newswire.ca)
  • 68. The method according to claim 67, wherein the monoclonal antibody is human or humanized. (freepatentsonline.com)
  • Alsmadi O and Tilley SA (1998) Antibody‐dependent cellular cytotoxicity directed against cells expressing human immunodeficiency virus type 1 enveloppe of primary or laboratory‐adapted strains by human and chimpanzee monoclonal antibodies of different epitope specificities. (els.net)
  • We found that adipose cells decreased the secretion of interferon-γ by natural killer cells, but did not alter natural killer cells' cytotoxicity. (inserm.fr)
  • A Pilot Trial of Humanized Anti-GD2 Monoclonal Antibody (hu14.18K322A) with Chemotherapy and Natural Killer Cells in Children with Recurrent/Refractory Neuroblastoma. (semanticscholar.org)
  • Not to be confused with Natural killer T cell . (wikipedia.org)
  • They were named "natural killers" because of the initial notion that they do not require activation to kill cells that are missing "self" markers of MHC class 1. (wikipedia.org)
  • In humans, CD27 is expressed on the surface of the majority of T cells, memory B cells and plasma cells, and some natural killer (NK) cells ( 4-6 ). (aacrjournals.org)
  • It does this by activating natural killer cells by binding to carbonic anhydrase IX. (wikipedia.org)
  • RESULTS: MEDI-563 binds to an epitope on IL-5Ralpha that is in close proximity to the IL-5 binding site, and it inhibits IL-5-mediated cell proliferation. (garvan.org.au)
  • Inhibition of integrin alpha 2 leads to an inhibition of cell-cell interactions, endothelial cell-matrix interactions, vascular endothelial cell proliferation and angiogenesis. (cancer.gov)
  • Monoclonal antibody (mAb) based therapies have had a tremendous impact on the treatment of cancer and, in particular, for lymphoma. (aacrjournals.org)
  • Here we discuss the existing strategies for targeting senescent cells and upcoming challenges in translating these strategies into safe and efficient therapies. (jci.org)
  • Our CliniMACS® Systems support investigators translating novel cell and gene therapies into clinical application. (miltenyibiotec.com)
  • Examples include cancer vaccines and CAR-T cell, and targeted antibody therapies. (wikipedia.org)
  • T-cell lymphoma (CTCL), and is sometimes applied to ultraviolet-tolerant early CTCL patients as one of the first-line therapies in the real world. (bioportfolio.com)
  • Included with this issue is our first of two supplements this year focused on cell therapies. (bioprocessintl.com)
  • One of her recent studies indicates that IFNy-production therapies could be effective adjuvants for antibody therapy for chronic lymphocytic leukemia. (osu.edu)
  • Phase II trial of the anti-G(D2) monoclonal antibody 3F8 and granulocyte-macrophage colony-stimulating factor for neuroblastoma. (mendeley.com)
  • PURPOSE: To describe oncolytic effects of treatment with anti-G(D2) monoclonal antibody 3F8 plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with neuroblastoma (NB). (mendeley.com)
  • The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO ® ) for the treatment of (i) metastatic Merkel cell carcinoma (mMCC) in adults and pediatric patients 12 years and older and (ii) patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. (newswire.ca)
  • Enhancement of antibody-dependent cell-mediated cytotoxicity by endowing IgG with FcαRI (CD89) binding. (astrazeneca.com)
  • For example, arguably the most common N-glycan structure present on mAbs made in Chinese hamster ovary (CHO) cells is G0F: asialo-, agalacto-, biantennary complex N-glycan, core-substituted with fucose. (biopharminternational.com)
  • The recent FDA approvals of the programmed cell death protein 1 (PD-1)-targeted checkpoint inhibitors pembrolizumab and nivolumab mark the latest successes in the rapidly expanding field of cancer immunotherapies. (frontiersin.org)
  • Approved checkpoint inhibitors include antibodies such as ipilimumab, nivolumab, and pembrolizumab. (wikipedia.org)
  • To determine the spectrum of antiviral antibodies in HIV-1-infected individuals in whom viral replication is spontaneously undetectable, termed HIV controllers (HICs). (ovid.com)
  • The identification of several donors with NK cell deficiencies, who were susceptible to severe and recurrent viral infections, provided evidence on the role of NK cells in the antiviral response, especially on herpes virus, hepatitis virus and poxvirus ( 5 , 6 ). (frontiersin.org)