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.
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 ( 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.
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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 ...
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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 ...
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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.
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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 ... Drugs that are a monoclonal antibody, Monoclonal antibodies, Abandoned drugs, All stub articles, Monoclonal antibody stubs, ... CAIX is expressed on the surface of most renal cancer cells and is hypothesized to be on the surface of other tumor cells. It ... Girentuximab (Rencarex) for renal cell carcinoma v t e v t e (CS1 errors: missing periodical, CS1 German-language sources (de ...
... (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 ... Wang, W; Erbe, AK; Hank, JA; Morris, ZS; Sondel, PM (2015). "NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in ... ISBN 1-55581-246-5. University of Leicester, Virus Immunopathology Notes Antibody-Dependent+Cell+Cytotoxicity at the US ...
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- ...
... 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 ...
This is thought to enhance its antibody-dependent cell-mediated cytotoxicity. It was first tested in humans in 2007. Kyowa ... Drugs that are a monoclonal antibody, Monoclonal antibodies, Orphan drugs, All stub articles, Monoclonal antibody stubs, ... 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 ...
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). ...
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 ...
Helps kill breast cancer cells that overexpress HER-2, possibly through antibody-dependent cytotoxicity. Clinical use: ... Mechanism of action: A monoclonal antibody that binds to the glycoprotein receptor IIb/IIIa on activated platelets, preventing ... Predisposes to infections (reactivation of latent TB). Mechanism of action: A monoclonal antibody to CD20 surface ... Mechanism of action: A monoclonal antibody to TNF, proinflammatory cytokine. Clinical use: Crohn's disease, rheumatoid ...
... 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: ... which activates CD4 Th2 cells and inhibits CD4 Th1 cell function. Many factors produced by other cells can regulate the ... With a diameter of 15-22 μm, monocytes are the largest cell type in peripheral blood. Monocytes are mononuclear cells and the ...
... 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 ...
... by being deposited on the cell surface of the pathogen. In antibody-dependent cell-mediated cytotoxicity the pathogen does not ... This allows the antibody binding of an immune effector cell via its Fc domain. Antibody-dependent cell-mediated inherent ... The Fab portion of the antibody binds to the antigen, whereas the Fc portion of the antibody binds to an Fc receptor on the ... eosinophils and NK cells). Lack of mediation can cause inflammation of surrounding tissues and damage to healthy cells. Thau, L ...
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 ( ...
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 ... Drugs that are a monoclonal antibody, Monoclonal antibodies for tumors, Sanofi). ... It is a monoclonal antibody that binds to CD52, a protein present on the surface of mature lymphocytes, but not on the stem ... Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro AJ, Waldmann H (October 1983). "Removal of T cells from bone marrow for ...
The mechanism of action includes B-cell lysis by antibody-dependent cellular cytotoxicity (ADCC), and complement-dependent ... complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC). Passive antibody therapy was ... complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC). Antagonism by antibodies ... For example, the ligation of CD40 monoclonal antibodies and CD40 on tumor cells license antigen-presenting cells (predominantly ...
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. In its ... 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 ...
... 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 ...
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 ...
... 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 ... Drugs that are a monoclonal antibody, Breakthrough therapy, GSK plc brands, Monoclonal antibodies for tumors, Orphan drugs, ... March 2019). "Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy ...
... 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), ... Drugs that are a monoclonal antibody, Monoclonal antibodies for tumors, Antibody-drug conjugates, Yttrium compounds, Indium ... Together, these actions eliminate B cells from the body, allowing a new population of healthy B cells to develop from lymphoid ...
... 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 ...
... 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- ...
Antibody-dependent cell-mediated cytotoxicity (ADCC) describes the cell-killing ability of certain lymphocytes, which requires ... The live-cell protease is only active in cells that have a healthy cell membrane, and loses activity once the cell is ... Lymphocyte-mediated cytotoxicity, on the other hand, does not have to be mediated by antibodies; nor does complement-dependent ... Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. ...
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 ...
... 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. ...
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 ...
8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity". Neurochem. Int. 64: 18-23. doi:10.1016/ ... dependent neuroprotection in mice after perinatal hypoxia and ischemia". CNS Neurol Disord Drug Targets. 12 (3): 360-70. doi: ... "A monoclonal antibody TrkB receptor agonist as a potential therapeutic for Huntington's disease". PLOS ONE. 9 (2): e87923. ... Cell Press (2015). "Molecule found in tree leaves helps female mice combat weight gain; males unaffected". ScienceDaily. ...
Natural killer (NK) cell cytotoxicity and the antigen-presenting function of dendritic cells diminishes with age. The age- ... T cells undergo deleterious age-dependent changes. This leaves the body practically devoid of virgin T cells, which makes it ... specialized in facilitating peripheral B cell maturation, and the generation of antibody-producing plasma cells and memory B ... T cells are not the only immune cells affected by aging: Hematopoietic stem cells (HSC), which provide the regulated lifelong ...
... and therefore does not induce the antibody-dependent cellular cytotoxicity that could be expected from this IgG1-type antibody ... Belimumab, sold under the brand name Benlysta, is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), ... When autoimmune B cells attack the body's own tissues, they are normally destroyed by cell suicide (apoptosis). Researchers ... Belimumab binds to BAFF and prevents it from binding to B cells. Without BAFF, B cells commit suicide and no longer contribute ...
Antibody binding to cell surface receptors and altering its activity Activation of the complement pathway. Antibody-dependent ... cellular cytotoxicity. The pathophysiology of type II hypersensitivity reactions can be broadly classified into three types: ... Omalizumab is a monoclonal antibody that interacts with the binding site of the high-affinity IgE receptor on mast cells. It is ... Type I: IgE mediated immediate reaction Type II: Antibody-mediated reaction (IgG or IgM antibodies) Type III: Immune complex- ...
This non-hemolytic defensin has been shown to have preferential cytotoxicity towards various cancer cells including B-cell ... dependent histone deacetylase SIRT1. ORCTL3 has been shown to be activated for apoptosis induction in renal cells in vitro, in ... during the same year when a separate study found that p53 had immunoreactivity with serum from tumors containing antibodies. ... causing cell death in cancer cells, but not normal cells. 3) E4orf4 may use oncogenes that have been activated in cancer cells ...
"Cell specific cytotoxicity and uptake of graphene nanoribbons". Biomaterials. 34 (1): 283-93. doi:10.1016/j.biomaterials. ... Thermally dependent resistivity in mesoscopic copper wire limits efficiency and current carrying capacity in small-scale ... The sensors bind to 8-hydroxydeoxyguanosine (8-OHdG) and is capable of selective binding with antibodies. The presence of 8- ... Receptors on the cancer cell membrane bind TRAIL and cell surface enzymes clip the peptide thus release the drug onto the cell ...
... for example by fusing B-cells with myeloma cells. The resulting "hybridoma" from this combination expresses a desired antibody ... "Cellular trafficking and cytotoxicity of anti-CD19-targeted liposomal doxorubicin in B lymphoma cells". Journal of Liposome ... Suchyna TM, Tape SE, Koeppe RE, Andersen OS, Sachs F, Gottlieb PA (July 2004). "Bilayer-dependent inhibition of ... Köhler G, Milstein C (August 1975). "Continuous cultures of fused cells secreting antibody of predefined specificity". Nature. ...
"A Recombinant Rabies Virus Expressing the Marburg Virus Glycoprotein Is Dependent upon Antibody-Mediated Cellular Cytotoxicity ... The mature progeny particles then infect other cells to repeat the cycle. A virus that fulfills the criteria for being a member ... The viral RNA-dependent RNA polymerase (RdRp, or RNA replicase) partially uncoats the nucleocapsid and transcribes the genes ... The filovirus life cycle begins with virion attachment to specific cell-surface receptors, followed by fusion of the virion ...
These TH2 cells interact with other lymphocytes called B cells, whose role is production of antibodies. Coupled with signals ... although they are still caused by release of mediators from eosinophils and are still dependent on activity of TH2 cells. ... cytotoxicity testing, urine autoinjection, skin titration (Rinkel method), and provocative and neutralization (subcutaneous) ... The immune system does not recognize the affected cells as normal parts of the body, causing a T-cell-mediated immune response ...
... enhances the antigen-dependent cell-mediated immunity. Spleen cell cytotoxicity is augmented to a significant degree. ... Conjugates with polytuftsin retain tuftsin-like effects and increase the epitope specific antibody production. Tuftsin sequence ... The number of antigen-forming cells increases following injections of tuftsin T-dependent antigen. ... Stimulation of pinocytosis is exerted only on phagocytic cells, not on cultured cell line mouse leukemia. The vertical motility ...
When dinutuximab binds to any cell that has GD2, that cell is destroyed via cell-mediated cytotoxicity and complement-dependent ... Each antibody is made of both mouse and human components and targets glycolipid GD2, expressed on neuroblastoma cells and on ... They differ in that dinutuximab is manufactured using mouse cells, and dinutuximab beta is manufactured using hamster cells. ... red blood cells, white blood cells, and albumin, hypotension, electrolyte imbalance including low sodium, potassium, and ...
IgG also plays an important role in antibody-dependent cell-mediated cytotoxicity (ADCC) and intracellular antibody-mediated ... IgG molecules are created and released by plasma B cells. Each IgG antibody has two paratopes. Antibodies are major components ... IgG antibodies can prevent IgE mediated anaphylaxis by intercepting a specific antigen before it binds to mast cell-associated ... IgG antibodies are generated following class switching and maturation of the antibody response, thus they participate ...
... antibody synthesis, cytotoxicity and regulation. The activation of the hypothalamic-pituitary axis (HPA axis) stimulates the ... immune cells that were administered high doses of methylprednisolone has been shown to inhibit respiration in a dose-dependent ... The dependency of house keeping cells and immune cells on ATP, results in immunosuppression during ATP deficit. Specific immune ... Mol Cell Endocrinol. 2011;336(1-2):23-30. doi:10.1016/j.mce.2010.12.001 Song IH, Buttgereit F (February 2006). "Non-genomic ...
The activity and cytotoxicity of NK cells is inhibited by the expression of sialic acids on the tumor cell surface. Removal of ... October 2009). "Sustained and NK/CD4+ T cell-dependent efficient prevention of lung metastasis induced by dendritic cells ... PBMC derived T cells activated for 5 days with anti-CD3 antibody and IL-2 also can be used for the purpose. In addition, human ... Not all cancer cells have cell entry receptors for the virus and not all cancer cells express virus processing serine proteases ...
Impaired NK-cell cytotoxicity is the hallmark of HLH. All genetic defects for familial HLH are related to granule-dependent ... the FDA approved the anti-IFN-gamma monoclonal antibody emapalumab (proprietary name Gamifant) for the treatment of pediatric ... mutations in genes that code for proteins cytotoxic T cells and NK cells use to kill targeted cells, such as those infected ... The blood count typically shows decreased numbers of blood cells-including a decreased number of circulating red blood cells, ...
"A novel HSV-2 subunit vaccine induces GLA-dependent CD4 and CD8 T cell responses and protective immunity in mice and guinea ... against HSV-2 superinfection of HSV-1 seropositive mice demonstrates protection by antibodies mediating cellular cytotoxicity ... only the HSV-tk transfected Hela cells were killed by the granciclovir, leaving the nonviral cells unharmed. The Hela cells ... When Hela cells were transfected with the HSV-tk gene, and were then put in a culture with nontransfected cells, ...
IFN-α/IFNγ producing activity of leukocytes and cytokines important in the development of cytotoxicity towards tumor cells. It ... Smaldone GT, Antelmann H, Gaballa A, Helmann JD (May 2012). "The FsrA sRNA and FbpB protein mediate the iron-dependent ... been found to significantly stimulate broad-spectrum immune activity including activation of secretion of specific antibodies ... van Dijl JM, Hecker M (January 2013). "Bacillus subtilis: from soil bacterium to super-secreting cell factory". Microbial Cell ...
Infertility after anti-sperm antibody binding can be caused by autoagglutination, sperm cytotoxicity, blockage of sperm-ovum ... One of these changes are to the uterine natural killer cells (uNK). NK cells, part of the innate immune system, are cytotoxic ... "Prenatal immune programming of the sex-dependent risk for major depression". Translational Psychiatry. 6 (5): e822. doi:10.1038 ... In the first trimester of pregnancy, uNK cells are among the most abundant leukocytes present, but the number of uNK cells ...
... eradicate HTLV-1 in combination with autologous peripheral blood mononuclear cells via antibody-dependent cellular cytotoxicity ... Tanaka Y, Takahashi Y, Kodama A, Tanaka R, Saito M (2014). "Neutralizing antibodies against human T cell leukemia virus type-I ... So, an increase in numbers of HTLV-1-infected cells using cell division, by actions of accessory viral genes, especially Tax, ... The human T-lymphotropic virus, human T-cell lymphotropic virus, or human T-cell leukemia-lymphoma virus (HTLV) family of ...
LCMV can be grown in a variety of cell lines including BHK21, L and Vero cells, and it may be identified with immuno- ... The introduced mouse will seroconvert, allowing use of immunofluorescence antibody (IFA), MFIA or ELISA to detect antibodies. ... The RNA-dependent, RNA-polymerase brought along with the virus initially binds to a promoter on the L and S segments and begins ... By the method of Cr-release cytotoxicity assay, thereby tagging the CTL with chromium-51 (Cr-51), the CTL destruction of ...
Cytotoxicity is primarily due to inhibition of topoisomerase II after the enzyme induces a break in DNA, preventing religation ... When taken up by a cell the four ring structure intercalates between DNA bases pairs while the sugar sits within the minor ... Trastuzumab (a HER2 antibody used to treat breast cancer) may enhance the cardiotoxicity of anthracyclines although the ... Anthracycline-mediated cardiotoxicity is dose-dependent and cumulative, with the damage imposed to heart occurring upon the ...
... binds directly to various integrin receptors in a cell type-dependent manner, including integrin αvβ3 in endothelial ... Chen CC, Young JL, Monzon RI, Chen N, Todorovic V, Lau LF (2007). "Cytotoxicity of TNFα is regulated by Integrin-Mediated ... Blockade of CYR61 by antibodies inhibits bone fracture healing in mice. In the kidney, CYR61 is expressed in podocytes in ... CYR61 is able to support cell adhesion, stimulate cell migration, promote growth factor-induced cell proliferation and ...
CSF is normally free of red blood cells and at most contains fewer than 5 white blood cells per mm3 (if the white cell count is ... Some authors dispute this, posing that there is no unidirectional CSF circulation, but cardiac cycle-dependent bi-directional ... Kwong KC, Gregory JM, Pal S, Chandran S, Mehta AR (2020). "Cerebrospinal fluid cytotoxicity in amyotrophic lateral sclerosis: a ... and specific antibodies such as aquaporin-4 may be tested for to assist in the diagnosis of autoimmune conditions. A lumbar ...
... and protein synthesis in cell-free systems and intact cells". Cancer Res. 36 (8): 2891-5. PMID 1277199. Archived from the ... The rate of cardiomyopathy is dependent on its cumulative dose, with an incidence about 4% when the dose of doxorubicin is 500- ... In 2006, animal research coupling a murine monoclonal antibody with doxorubicin created an immunoconjugate that was able to ... It may also increase quinone type free radical production, hence contributing to its cytotoxicity. The planar aromatic ...
Sadelain has referred to CAR T cells as a "living drug." A CAR typically comprises an antibody fragment (scFv) to recognize the ... "Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRζ /CD28 receptor"doi10.1038/nbt0102- ... "Antigen-dependent CD28 Signaling Selectively Enhances Survival and Proliferation in Genetically Modified Activated Human ... CAR T cells are made by extracting a cancer patient's T cells, inserting a CAR into the cell using a vector such as a gamma- ...
... 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 ... an antibody can signal immune cells to present antibody fragments to T cells, or downregulate other immune cells to avoid ... The "knobs-into-holes" shape facilitates antibody dependent cell mediated cytotoxicity. Single chain variable fragments (scFv) ...
Direct and antibody dependent cell mediated cytotoxicity against Giardia lamblia by splenic and intestinal lymphoid cells in ... Direct and antibody dependent cell mediated cytotoxicity against Giardia lamblia by splenic and intestinal lymphoid cells in ... Direct and antibody dependent cell mediated cytotoxicity against Giardia lamblia by splenic and intestinal lymphoid cells in ...
... for therapeutic antibodies, particularly when evaluating their potential for effector functions. ... Cell-based assays play an important role in determination of mechanism of action (MOA) ... EU PEGS] Quantify Antibody-Dependent Cell Phagocytosis (ADCP): Application of a Robust, Non-Radioactive KILR Cytotoxicity ... Tools & Resources / Document Resource Library / Documents / [EU PEGS] Quantify Antibody-Dependent Cell Phagocytosis (ADCP): ...
Antibody dependent cell mediated cytotoxicity and erythrophagocytosis assays in Rh haemolytic disease of the newborn. The ... Antibody dependent cell mediated cytotoxicity and erythrophagocytosis assays in Rh haemolytic disease of the newborn. ... OBJECTIVE: To evaluate the role of antibody dependent cell mediated cytotoxicity (ADCC) and erythrophagocytosis in comparison ... Cord blood monocytes were used as effector cells in both the assays. RESULTS: Good correlation (P , 0.01) was observed between ...
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC). Antibody-dependent cell-mediated cytotoxicity is the process when ... Antibody-dependent cell cytotoxicity: immunotherapy strategies enhancing effector NK cells. Immunol Cell Biol (2017) 95:347-55 ... D) Autoantibodies binding to effector cell with Fc receptors (FcRs) can trigger antibody-dependent cell-mediated cytotoxicity ( ... Involvement of antibody-dependent cell-mediated cytotoxicity in inflammatory demyelination in a mouse model of neuromyelitis ...
... receptors have been proposed to modulate the in vivo cytotoxic response against tumor targets for both spontaneous and antibody ... dependent pathways. Using a variety of syngenic and xenograft models, we demonstrate here that the inhibitory FcgammaRIIB ... Mice deficient in FcgammaRIIB showed much more antibody-dependent cell-mediated cytotoxicity; in contrast, mice deficient in ... here that the inhibitory FcgammaRIIB molecule is a potent regulator of antibody-dependent cell-mediated cytotoxicity in vivo, ...
Antibodies, Monoclonal; *Antibody-Dependent Cell Cytotoxicity; Binding Sites; Cell Line; Epitopes; Gene Products, env; *HIV ... HIV-1 Env-specific binding antibody, neutralizing antibody, antibody-dependent cell-mediated cytotoxicity (ADCC), and profiles ... Antibody-dependent cell-mediated cytotoxicity directed by a human monoclonal antibody reactive with gp120 of HIV-1. ... We used a human monoclonal antibody (MAb; 15e) to identify an antibody-dependent cell-mediated cytotoxicity (ADCC) epitope on ...
Human NK cells lyse Ab-coated target cells through the process of Ab-dependent cellular cytotoxicity (ADCC). Improving ADCC ... Blocking NK Cell Inhibitory Self-Recognition Promotes Antibody-Dependent Cellular Cytotoxicity in a Model of Anti-Lymphoma ...
The immune effector cell mechanisms include antibody-dependent cellular cytotoxicity and antibody-dependent cellular ... Alemtuzumab is a humanized monoclonal antibody against CD52, an antigen found on B-cells, T-cells, and almost all CLL cells. It ... Monoclonal Antibodies. Class Summary. Monoclonal antibodies are antibody proteins that are produced from a particular lineage ... Idelalisib induces apoptosis and inhibits proliferation in cell lines derived from malignant B cells and in primary tumor cells ...
Antibody-dependent cell-mediated cytotoxicity to hemagglutinin of influenza A viruses after influenza vaccination in humans ...
Categories: Antibody-Dependent Cell Cytotoxicity Image Types: Photo, Illustrations, Video, Color, Black&White, PublicDomain, ...
... technology to boost the antibodys ADCC anti-tumor activity.The GlymaxX® technology for production of afu... ... Keywords: Antibody-Dependent Cell Cytotoxicity; Fucose; Sugars; Antibodies; Glycoproteins; Glycosylation; Cell Line; Antibody- ... The absence of fucose enhances ADCC (antibody-dependent cell-mediated cytotoxicity) activity for antibodies directed against ... to the N-linked antibody carbohydrate part by antibody producing cells. ...
Monoclonal antibodies (mAbs) target only cell surface antigens and can induce antibody-dependent cellular cytotoxicity (ADCC) ... Immune effects through antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytolysis - Binding the antibody ... B cells are lymphoid cells that serve as professional APCs but also secrete antibodies in response to a foreign antigen. ... Nonconjugated antibodies can also induce cell death if they crosslink a cell surface receptor that can initiate a downstream ...
... kill certain tumour cells and have appropriate receptors for antibody-dependent cell-mediated cytotoxicity. ... Dendritic cells. These cells present antigen to T cells, and stimulate cell proliferation and the immune response. ... Effector T cells fall into two classes - CD8+ killer or cytotoxic T cells, which destroy infected cells, and CD4+ or helper T ... A large and diverse set of recognition molecules - antibodies (produced by B cells) and T-cell receptors - mediate adaptive ...
Two methods for measuring the activity of antibody-dependent cell-mediated cytotoxicity are compared. One of them is based on ... Comparative analysis of methods of evaluating antibody-dependent cell-mediated cytotoxicity].. *Z. Karaev, E. Golikova ...
Antibody-dependent cellular cytotoxicity (ADCC), has been shown to be independent in vitro of thymus-derived lymphocytes, but ... The presence of thymus-dependent (T) cells is controversial. Bone marrow cells obtained from healthy volunteers was ... Human antibody-dependent cellular cytotoxicity. Isolation and identification of a subpopulation of peripheral blood lymphocytes ... Human antibody-dependent cellular cytotoxicity. Isolation and identification of a subpopulation of peripheral blood lymphocytes ...
M2e antibodies are non-neutralising and are thought to mediate protection via antibody-dependent cell cytotoxicity (ADCC) [92 ... used B cell screening to identify cross-reactive antibodies targeting conserved regions of the HA that could be frequently ... Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuramini-dase-Reactive Antibodies. Cell 2018, 173 ... Defining and Manipulating B Cell Immunodominance Hierarchies to Elicit Broadly Neutralizing Antibody Responses against ...
Antibody-dependent cell-mediated cytotoxicity ________. is particularly important for killing microbes that are too large be ... cell types is involved in cell-mediated immunity. T regulatory cells,T helper cells,TH1 cells andT cytotoxic cells ... stem cells to B cells to plasma cells Which of these statements is not true of antibody molecules. Antibody molecules can ... ability to form cells that directly kill virus-infected host cells T helper cells they activate B cells,they have CD4 molecules ...
... antibody-dependent cellular cytotoxicity). ADCC is an Fc-dependent mode of action (MoA) by which antibodies mediate tumor cell ... Understanding the response of tumor cells to antibodies with Fc-dependent MoA has the potential to improve the efficacy of ... Tumor-specific T cells and antibodies have been detected in these patients, which suggests that the ADCC-competent antibodies ... as well as tumor cell-intrinsic molecular features that impact the cells sensitivity to ADCC-competent antibodies. To identify ...
Reimagining antibody-dependent cellular cytotoxicity in cancer: the potential of natural killer cell engagers ... Reimagining antibody-dependent cellular cytotoxicity in cancer: the potential of natural killer cell engagers ... Identifying disease-critical cell types and cellular processes by integrating single-cell RNA-sequencing and human genetics ... Cell Genomics, Juulia J. Partanen; Paavo Häppölä; Wei Zhou; Arto Lehisto; Mari Ainola; Eva Sutinen; Richard J. Allen; Amy ...
In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and ... Ginsenoside Rh2-mediated G1 phase cell cycle arrest in human breast cancer cells is caused by p15 Ink4B and p27 Kip1-dependent ... Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells. ... A formulated red ginseng extract rescues PC12 cells from PCB-induced oxidative cell death through Nrf2-mediated upregulation of ...
Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated ... showed signs of B-cell return with counts ,10 cells/µL. By Month 18, most patients (87%) had counts ,10 cells/µL. ... The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the ... A response to pneumococcal vaccination (a T-cell independent antigen) as measured by an increase in antibody titers to at least ...
Applications of the KILR Cytotoxicity Assays 1. Antibody dependent cell-mediated cytotoxicity (ADCC) ... the target cells express the KILR reporter construct inside the cells. Death of the cells leads to rupture of the cell membrane ... Transduction of adherent cells to generate KILR cell lines, for use in immune-mediated cytotoxicity assays. ... This results in a high level of expression of the fusion protein inside the target cells. Target cell death in a cytotoxicity ...
... is antibody-dependent cell-mediated cytotoxicity (ADCC).. In ADCC, circulating natural killer (NK) cells perform lytic killing ... Non-Ab dependent or spontaneous lysis of cells increases background and decreases the dynamic antibody-specific signal range. ... Cells as Reagents. In our ADCC reporter bioassay, effector cells are essentially assay reagents. The Jurkat effector cells are ... in Jurkat cells and is activated in NK cells upon cross linking of FcγRIIIa receptor with target cell-bound specific antibody. ...
Likely mechanisms of action include antibody-dependent cell-mediated cytotoxicity, complement-mediated cytotoxicity, and ... Given that most cancers may be caused by random mutations arising from stem cell divisions of normal self-renewing cells, ... Unlike CTLA-4, which is expressed exclusively on T cells and normally counteracts the activity of the T-cell costimulatory ... Gemtuzumab ozogamicin, a humanized IgG4 monoclonal antibody coupled with calicheamicin, in 2000 became the first antibody drug ...
... the immune effector cell mechanisms include antibody-dependent cellular cytotoxicity and antibody-dependent cellular ... an effect that may lead to a low number of blood cells such as red cells, white cells, and platelets. This effect can cause ... CD20-directed cytolytic antibody; upon binding to CD20, obinutuzumab mediates B-cell lysis through 1) engagement of immune ... Patients on chemotherapy with anti-B cell antibodies should wait =6 months after therapy before being vaccinated with ...
Novel TLR 7/8 agonists for improving NK cell mediated antibody-dependent cellular cytotoxicity (ADCC) Authors: V Khanna, H Kim ... Combining adoptive NK cell infusion with a dopamine-releasing peptide reduces senescent cells in aged mice Authors: Z Bai, P ... Cell Death & Disease, 2022;13(4):305.. Species: Human. Sample Types: Cell Culture Supernates. ... T cell responses when co-incubate with a cancer cell with mAb stimulation. ...
T cells may be responsible for regulating the proliferation, and thus the growth, of malignant epithelial cells in BCC. La ... The lymphocytic infiltrate revealed in parts a pattern of a small lymphocytic follicle with peripherally situated T cells and ... The predominance of Tlymphocytes in BCC suggests a local cell-mediated immune response. However, the presence of B-lymphocytes ... The results showed that the dense lymphocytic infiltrate surrounding neoplastic cells of BCC consisted chiefly of T-lymphocytes ...
Enhancement of antibody-dependent cell mediated cytotoxicity: a new era in cancer treatment. Immunotargets and Therapy. 2015; 4 ... The engagement of CTLA-4 on primary melanoma cell lines induces antibody-dependent cellular cytotoxicity and TNF-α production. ... Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients. ... but also in tumor cells, might facilitate tumor cellular lysis through an IPI-dependent cell-mediated cytoxicity by FcRγ ...
  • OBJECTIVE: To evaluate the role of antibody dependent cell mediated cytotoxicity (ADCC) and erythrophagocytosis in comparison to IgG subtypes and concentration of anti-D in haemolytic disease of the newborn (HDN). (
  • 15e) to identify an antibody-dependent cell-mediated cytotoxicity (ADCC) epitope on HIV-1 gp120. (
  • Using a standard ADCC assay, 15e was found to mediate ADCC against cells infected with HIV-1IIIB but not HIV-1RF. (
  • 15e did not mediate ADCC against cells with recombinant gp120 bound to surface CD4, indicating that 15e does not mediate innocent bystander ADCC against uninfected CD4 cells. (
  • To better define the 15e epitope, we performed ADCC against target cells infected with a vaccinia vector which expresses processed HIV-1IIIB gp160 from which the third variable region was deleted (amino acids, 312-328). (
  • MAb 15e efficiently mediated ADCC against cells expressing this altered form of gp120, indicating that this region is not contributing to the conformational epitope defined by 15e. (
  • The absence of fucose enhances ADCC (antibody-dependent cell-mediated cytotoxicity) activity for antibodies directed against cancer and infectious diseases. (
  • Our research focuses on anti-tumor antibodies that target tumor cells via ADCC (antibody-dependent cellular cytotoxicity). (
  • ADCC is an Fc-dependent mode of action (MoA) by which antibodies mediate tumor cell lysis and phagocytosis by innate effector cells, including NK cells and macrophages. (
  • The clinically-approved ADCC-competent antibodies Rituximab, Daratumumab and Obinutuzumab have achieved moderate to high response rates in patients. (
  • Only a small number of patients on ADCC-competent antibody therapies remain tumor-free for decades. (
  • Tumor-specific T cells and antibodies have been detected in these patients, which suggests that the ADCC-competent antibodies induced immunological memory against tumor antigens (the vaccinal effect). (
  • Several recent studies demonstrated that the vaccinal effect can be achieved in murine models by enhancing the ADCC activity or by combining ADCC-competent antibodies with immune modulatory agents. (
  • Our exploratory research is focused on identifying and characterizing factors that modulate immune cell activation (i.e., enhance the vaccinal effect) as well as tumor cell-intrinsic molecular features that impact the cell's sensitivity to ADCC-competent antibodies. (
  • Furthermore, by dissecting the mechanism of immune effector cell activation by ADCC-competent antibodies, we hope to achieve long-term immunological memory and durable response in patients. (
  • An important and desirable biological activity of most antibody drugs, especially for oncology targets, is antibody-dependent cell-mediated cytotoxicity (ADCC). (
  • In ADCC, circulating natural killer (NK) cells perform lytic killing of antigen-bearing target cells through specific antibody cross-linking of the two cell types. (
  • Assays that use primary NK cells possess large inherent variability because of the significant influence of genetic variability and blood donor health status on the extent of ADCC mediated by these cells. (
  • Promega's reporter-based ADCC bioassay is a new cell-based genetic reporter assay that uses an engineered Jurkat cell line as the effector cell population, avoiding the requirement of purified NK cells from blood donors and avoiding the variability in effector function. (
  • We also engineered the same Jurkat cell line to co-express the FcγRIIIa receptor (high affinity variant), thus completing the engineering needed to generate an effector cell line able to quantify Fc effector function of therapeutic antibodies in ADCC. (
  • In our ADCC reporter bioassay, effector cells are essentially assay reagents. (
  • With the improved assay design and procedure, and cells as reagents, the new reporter-based bioassay format outperforms classic ADCC in many key parameters: low variability, improved accuracy and precision, ease of assay procedure, and low background (sensitivity). (
  • Specificity of the reporter ADCC bioassay: Serial dilutions of Rituximab (anti-CD20 chimeric monoclonal antibody drug), Trastuzumab (anti-Her2 humanized monoclonal antibody drug), or assay medium control (no antibody) were incubated for 6 hours of induction at 37°C with engineered Jurkat effector cells, with or without WIL2-S target cells, as indicated. (
  • NK and antibody-dependent cell cytotoxicity (ADCC) has traditionally been assessed by the release of radioactive chromium from target cells following lysis. (
  • Serum IgA interacts with an Fc receptor called FcαR1 triggering antibody-dependent-cell-mediated cytotoxicity (ADCC). (
  • Antibody-dependent cell-mediated cytotoxicity (ADCC) contributes to clinical efficacy of a broad range of therapeutic antibodies. (
  • Classic ADCC cytotoxicity assays rely on primary effector cells, which are highly heterogeneous and variable. (
  • Binding of CAN04 to IL1RAP also allows NK-cells to recognize tumor cells and subsequent killing by antibody dependent cellular cytotoxicity (ADCC). (
  • CD16 binds aggregated IgG or IgG-antigen complex which functions in NK cell activation, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). (
  • B-cells produce anti-tumour antibodies, which can potentially mediate antibody-dependent cellular cytotoxicity (ADCC). (
  • Binding of proteinase 3 and myeloperoxidase to endothelial cells: ANCA-mediated endothelial damage through ADCC? (
  • In addition, we investigated whether interaction of PR3 or MPO with HUVEC monolayers also resulted in antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by anti-neutrophil cytoplasmic antibody (ANCA)-positive patient sera or rabbit IgG anti-PR3 or anti-MPO. (
  • Antibody-Dependent Cell Cytotoxicity (ADCC) assays that measure cell death often have low signal to background ratios and suffer from this donor variability of the PBMCs. (
  • NJ Bio has the capability of performing assays that will examine the ADCC activity of your therapeutic antibody. (
  • A bioluminescent ADCC reporter assay is used to determine whether your antibody will illicit an immune mediated cancer cell killing. (
  • Client will supply the antibody for this ADCC assay. (
  • Mouse monoclonal antibodies, as well as the humanized, clinically effective therapeutic agents trastuzumab (Herceptin(R)) and rituximab (Rituxan(R)), engaged both activation (FcgammaRIII) and inhibitory (FcgammaRIIB) antibody receptors on myeloid cells, thus modulating their cytotoxic potential. (
  • In order to gain more insight into the tumour-host relationship, the present study was conducted to characterize the in situ phenotype of the lymphocytic infiltrate surrounding tumour tissue of BCC through the use of monoclonal antibodies against B and T cell populations. (
  • Despite this great potential and in contrast to monoclonal antibodies (MAbs) of the IgG isotype, their development as research tools or human therapeutics has been scarce. (
  • Moreover, IL-21's antitumor activity can be potentiated by its combination with other immune-enhancing molecules, monoclonal antibodies recognizing tumor antigens, chemotherapy, or molecular targeted agents. (
  • Monoclonal Antibodies, Anti-asthmatics. (
  • Recently, pharmacological agents targeting eosinophilic traits in uncontrolled eosinophilic asthma, especially monoclonal antibodies directed against interleukins (IL-5, IL-4, IL-13) or their receptors, have shown promising results. (
  • glutamyl transpeptidase with monoclonal antibodies. (
  • I Preparation and characteristics of monoclonal antibodies to. (
  • Immunofluorescence imaging has provided captivating visual evidence for numerous cellular events, from vesicular trafficking, organelle maturation and cell division to nuclear processes including the appearance of various proteins and chromatin components in distinct foci in response to DNA damaging agents. (
  • 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. (
  • Kimura H, Sakai K, Arao T, et al: Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. (
  • Elotuzumab shows a dual mechanism of action that includes the direct activation of natural killer (NK) cells and the induction of NK cell-mediated antibody-dependent cellular cytotoxicity. (
  • Natural killer cell mediated-antibody-dependent cellular cytotoxicity induces concentration dependent target cell death, granzyme production. (
  • The drug has shown antitumor activity in multiple myeloma cells and mediated killing of tumor cells through MMAF-induced apoptosis, as well as by tumor cell lysis through antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis. (
  • The PGT121 BnAb, which recognizes an epitope consisting of the V3 loop and envelope glycans, mediates antibody-dependent cellular cytotoxicity and neutralization of cell-to-cell HIV-1 transmission. (
  • Immunosuppressive, delayed hypersensitivity, and cellular cytotoxicity tests are suppressed to a greater degree than antibody responses. (
  • CD62L is rapidly shed from lymphocytes and neutrophils upon cellular activation and the expression levels of CD62L (in conjunction with other markers) have been used to distinguish naïve, effector, and memory T cells. (
  • The Rho family of GTP-binding proteins has been implicated in the regulation of various cellular functions including actin cytoskeleton-dependent morphological change. (
  • In this immune reaction, antibody immunosuppressive, immunostimulatory, and autoim- is directed against a person's own cellular surface anti- mune. (
  • Cell-based assays play an important role in determination of mechanism of action (MOA) for therapeutic antibodies, particularly when evaluating their potential for effector functions. (
  • IMSEAR at SEARO: Antibody dependent cell mediated cytotoxicity and erythrophagocytosis assays in Rh haemolytic disease of the newborn. (
  • Cord blood monocytes were used as effector cells in both the assays. (
  • The KILR Retroparticles provide a potent vehicle for the stable delivery of the KILR reporter construct into almost any dividing cell line, enabling the creation of KILR cytotoxicity assays in the cell line expressing the target of your choice. (
  • Some High Performance Assays are additionally validated for cell culture supernatants, milk, saliva, or urine, as indicated on the individual product data sheets. (
  • These assays are laborious and require substantial quantities of patient blood to detect minor changes in cell lysis. (
  • CTL has previously shown that it can achieve similar results as with chromium release assays by directly imaging fluorescently-labelled target cells and visualising the loss of fluorescence signal upon cytolytic activity. (
  • Learn about PathHunter® checkpoint receptor assays (cell lines and bioassays) for innate and adaptive immunity. (
  • Assays discussed include functional cell-based assays for immunoglobulin and TNFR superfamilies like CD28, ICOS, PD1, CD47, SIRPα, and OX40 and assays for testing agonist antibodies (clustering and binding assays for bi-specifics). (
  • Learn how KILR® cytotoxicity assays provide a simple, non-radioactive and dye free method to specifically measure target cell death in a co-culture with effector cells. (
  • Assays for cancer immunotherapy drugs need to detect target cancer cell death when co-cultured with immune effector cells. (
  • PBMC effector cells have inherent donor variability, reducing their consistency and reproducibility in lot release assays. (
  • Discover how the cell-based, SPRINTer™ protein turnover biosensor assays can be used to rapidly screen small molecule therapeutics and quantify changes in endogenous protein levels in disease relevant cell models. (
  • Learn how InCELL cell-based binding assays can be used to detect compound cell entry and engagement to specific targets including enzymes, PROTACs, and epigenetic, plasma membrane, and ER proteins. (
  • Learn how functional cell-based assays support COVID-19 drug discovery programs, particularly in managing proinflammatory cytokines associated with high mortality rate in COVID-19 patients. (
  • Listen to several case studies for our target-specific, MOA-reflective cell based assays for small molecules and biologic therapeutics to accelerate your drug development through QC Lot Release programs for COVID-19 research. (
  • Utilize these easy-to-use cell-based, reporter gene assays to understanding the MOAs of therapeutics targeting TNFα, PD-1, IL-6, CD4, and RANK receptors. (
  • NJ Bio utilizes plate-based assays to characterize the ability of compounds to promote or inhibit cell proliferation, establish the cytotoxicity of compounds by measuring live/dead cells. (
  • NJ Bio utilizes in vitro cell cytotoxicity assays to analyze the potency of toxins or antibody-drug conjugates (ADCs). (
  • These assays quantitate ATP released by surviving cells at the end of the experiment, which directly reflects cell viability. (
  • NJ Bio offers classic 2D and novel 3D cytotoxicity assays, which provide comprehensive in vitro analysis of your ADC. (
  • The 3D assays utilize spheroids to mimic the physiological tumor microenvironment in comparison to the 2D assays where the cells adhere to the bottom of the well. (
  • Depending on your analyte, certain antibody combinations and assays can be designed to meet your needs. (
  • We will work with you directly to design assays specific to your analyte(s), whether it be an antibody or a more complex protein. (
  • In-vitro immunoassays , such as proliferation and cytotoxicity assays are routinely performed using these cells. (
  • T cells may be responsible for regulating the proliferation, and thus the growth, of malignant epithelial cells in BCC. (
  • Indeed, it costimulates T and natural killer (NK) cell proliferation and function and regulates B cell survival and differentiation and the function of dendritic cells. (
  • In addition, IL-21 exerts divergent effects on different lymphoid cell leukemia and lymphomas, as it may support cell proliferation or on the contrary induce growth arrest or apoptosis of the neoplastic lymphoid cells. (
  • Early studies showed that IL-21 costimulates the proliferation of B, T, and NK cells and mediates the differentiation of activated NK cells into more potent effector cells [ 2 ] (Figure 1 ), suggesting that IL-21 may represent a potentially useful agent for the development of tumor immunotherapies. (
  • IL-21 exerts complex effects on human and mouse B cell proliferation and survival as it can mediate apoptosis of B cells activated via toll like receptor (TLR) signals [ 10 , 13 ]. (
  • On the contrary it induces B cell proliferation in the presence of appropriate cosignals delivered by B cell receptor (BCR) stimulation and CD40 ligand (L) expressed by T helper (Th) cells [ 10 , 14 ]. (
  • The 3G8 antibody clone blocks neutrophil phagocytosis and stimulates NK cell proliferation. (
  • Additional reported applications (for the relevant formats) include: immunohistochemical staining of acetone-fixed frozen tissue sections 6 , immunoprecipitation 3 , stimulation of NK cell proliferation 4 , blocking of phagocytosis 5 , and blocking of immunoglobulin binding to FcγRIII 7,8 . (
  • Breast adenomyoepitheliomas are composed of a biphasic proliferation of myoepithelial cells round small epithelial-lined areas. (
  • Curcumol reduced the proliferation of breast cancer cells by targeting NCL/ERα36 and inactivating the PI3K/AKT pathway' - See curcumin at . (
  • When hosts suffer influenza virus infection, the TNFSF14-HVEM signaling pathway can stimulate the maturation and proliferation of memory CD8+ T cells, which helps the host immune system stimulate a second immune response against respiratory virus infection. (
  • Inhibitory receptors have been proposed to modulate the in vivo cytotoxic response against tumor targets for both spontaneous and antibody-dependent pathways. (
  • These results demonstrate that Fc-receptor-dependent mechanisms contribute substantially to the action of cytotoxic antibodies against tumors and indicate that an optimal antibody against tumors would bind preferentially to activation Fc receptors and minimally to the inhibitory partner FcgammaRIIB. (
  • Evidence currently suggests that the mechanisms responsible for resistance to cytotoxic agents generally do not confer resistance to immune-mediated mechanisms of tumor-cell killing. (
  • Cytotoxic T Lymphocyte Antigen 4 (CTLA-4 or CD152) exerts inhibitory activity on T cells, and since its oncogenic role in the progression of different types of tumors, it has emerged as a potential therapeutic target in cancer patients. (
  • Among IL-21 sensitive genes, Gzma and Gzmb encode for granzymes, involved in the activity of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. (
  • This suggests there is value in focusing on how to utilise a targeted cytotoxic approach with T cells for better patient outcomes. (
  • NK cells have cytotoxic small granules, which contain special proteins such as perforins and proteases, are known as granzymes in their cytoplasm. (
  • Outcomes HHT and ETP display synergistic cytotoxicity in AML cells ETP and HHT are cytotoxic reagents for AML cells.21,22 To check whether ETP and HHT possess synergistic cytotoxicity in AML cells, the chemosensitive AML super model tiffany livingston cell lines (THP1 MK-8776 inhibition and HL60) were treated with HHT and ETP alone or in combination (10/1 and 20/2, nM/M) for 48 hours. (
  • NK cell subsets and cytotoxic capacity of NK cells were decreased in severe patients. (
  • Target cell death in a cytotoxicity assay results in the release of the ePL-tagged protein into the medium. (
  • In order to further reduce the amount of cell material required and detect the effect of NK cells on different target cell lines, CTL has now developed a multi-colour cytotoxicity detection assay. (
  • Mice are DNA immunized with a plasmid expressing the antigen, and IgG-producing hybridomas are screened using a neutralizing assay based on engineered cell lines ( HEK-Blue™ Cells ). (
  • Learn about the first commercially-available SIRPα/CD47 cell-based assay -- PathHunter SIRPα Signaling Assay. (
  • Learn how KILR® CD16 effector cells ensure assay reproducibility with higher signal to background ratios, without worrying about donor variability. (
  • Exosomes were extracted from bone marrow mesenchymal stem cells (BMSC-Exos) where ALKBH5 inhibition assay was conducted to verify their function in the biological characteristics of TNBC cells. (
  • Needlessly to say, the trypan blue exclusion assay demonstrated a dose-dependent decease of cell viability by treatment of HHT and ETP by itself (Amount 1A). (
  • In particular, Toll-like receptors have been implicated in the development of B-cell autoimmunity, and genetic associations in Toll-receptor signalling pathways have been found in systemic lupus erythematosus. (
  • Innate immunity includes the role of toll-like receptors (TLRs) in improving antitumor and vaccine responses, muramyl tripeptide phosphatidylethanolamine (MTP-PE) in osteosarcoma, and natural killer (NK) cell-killer immunoglobulinlike receptor (KIR) mismatch. (
  • We have exploited activation of the NFAT signaling pathway, which is intact in Jurkat cells and is activated in NK cells upon cross linking of FcγRIIIa receptor with target cell-bound specific antibody. (
  • In a mouse lung metastasis model, inhibition of C5a, C5a receptor-1 (C5aR1) or NETosis reduced the number of circulating-tumor cells (CTCs) and the metastatic burden. (
  • Interleukin- (IL-) 21 was identified in 2000 as a CD4 + T cell-derived cytokine and the ligand of an IL-2R β -related orphan receptor [ 1 , 2 ], now defined as IL-21R. (
  • Benralizumab is a humanized monoclonal antibody (IgG1/κ-class) selective for interleukin-5 receptor alpha subunit (IL-5Rα). (
  • Additionally, NK cells contribute to the adaptive immune response by linking innate and the adaptive immunity through their receptor FcγRIIIA (CD16). (
  • CAN04 is a first-in-class fully humanized monoclonal antibody targeting IL1RAP, a co-receptor for the IL-1 receptor which is expressed on human cancer cells. (
  • In the area of adoptiveT cell transfer (ACT), which includes tumour infiltrating lymphocytes (TIL), CAR-T and T cell receptor therapy (TCR), clinical data has shown that T cell function is a strong predictive marker of immunotherapy response and patient health 2 . (
  • Isatuximab (anti-CD38) (SAR650984, hu38SB19) is an IgG1-derived monoclonal antibody that binds to a specific extracellular epitope of CD38 receptor with a kd of 0.12 nM. (
  • Cynarin blocks the interaction between the CD28 of T-cell receptor and CD80 of antigen presenting cells. (
  • The mouse monoclonal antibody 3G8 recognizes an extracellular epitope of CD16, a low affinity receptor for aggregated IgG (FcgammaRIII antigen). (
  • The technology of adoptive transfer of T-cell receptor (TCR) engineered T cells is wildly investigated as it has the potential to treat solid cancers. (
  • On this research, we discovered that dsDNA induced dose- and time-dependent enhance in IFN-α and Toll-like receptor 7 (TLR7), TLR9 and IRF7 expression in pDCs. (
  • However, the mechanisms underlying receptor-dependent regulation of Rho family members remain incompletely understood. (
  • We determined anti-SARS-CoV-2 receptor-binding domain immunoglobulin G (anti-RBD IgG), surrogate virus neutralization test (sVNT), T-cell subsets, and neutralization of wild-type, BA.1 and BA.5. (
  • [3] The underlying mechanism involves immunoglobulin E antibodies (IgE), part of the body's immune system, binding to an allergen and then to a receptor on mast cells or basophils where it triggers the release of inflammatory chemicals such as histamine . (
  • Although many mechanisms have been proposed to account for the anti-tumor activities of therapeutic antibodies, including extended half-life, blockade of signaling pathways, activation of apoptosis and effector-cell-mediated cytotoxicity, we show here that engagement of Fcgamma receptors on effector cells is a dominant component of the in vivo activity of antibodies against tumors. (
  • in contrast, mice deficient in activating Fc receptors as well as antibodies engineered to disrupt Fc binding to those receptors were unable to arrest tumor growth in vivo. (
  • Several signaling pathways are activated in the NK effector cells as a result of multiple FcγRIIIa receptors being engaged by the target cell-bound antibodies. (
  • The effector cell is a "killer" cell possessing Fc receptors. (
  • The integration of pathogen-associated molecular patterns (PAMPs) from microorganisms with their surface receptors in the immune cells, induces the production of several cytokines and chemokines that presents either a pro- and/or anti-inflammatory role by stimulating the secretion of a great variety of antibody subtypes and the activation of mechanisms of controlling the disease, such as the regulatory T cells. (
  • One vial containing 420 mg of trastuzumab, a humanised IgG1 monoclonal antibody produced by mammalian (Chinese hamster ovary) cell suspension culture and purified by chromatography including specific viral inactivation and removal procedures. (
  • PBMCs were incubated with one of three anti-CD20 antibodies: Ab-1 (IgG1), Ab-2 (IgG1) or a negative control Ab-3 (IgA2). (
  • The antibody component is an afucosylated IgG1 directed against BCMA, a protein expressed on normal B lymphocytes and multiple myeloma cells. (
  • A nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (COVITRAP) was developed to strengthen other COVID-19 preventive arsenals. (
  • Its intranasal administration in rats did not yield any detected circulatory levels of the human IgG1 anti-SARS-CoV-2 antibodies at any time point during the 120 hours of follow-up. (
  • Studies investigating the presence of autoantibodies in depression have focused in those targeting peripheral organs like the thyroid and intracellular antigens such as antinuclear antibodies and ribosomal-P antibodies ( 21 - 25 ). (
  • Besides anti-tumour antigen (TAA) antibodies, cancer patients also produce autoantibodies that bind to self-antigens. (
  • Each ADC will be tested against a variety of cancer cell lines expressing the targeted surface antigens and normal cell lines to evaluate in vitro safety. (
  • 1] They with a binding motif, which is determined by recognize specific structures on the surface of peptide length, and a.a. residues called anchor target cells as their antigens, which are composed residues. (
  • With the approval of Carvykti and other chimeric antigen T cell (CAR-T) therapies, there is an emergence of cell-based strategies using a more personalised treatment approach. (
  • Belantamab mafodotin-blmf is a first-in-class, anti-B-cell maturation antigen therapy indicated for adults with relapsed or refractory multiple myeloma who have received at least 4 prior therapies. (
  • Belantamab mafodotin-blmf is a first-in-class, anti-B-cell maturation antigen(BCMA) therapy indicated for adults with RRMM who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. (
  • Depending on the targeted antigen, cell panels specific to your antibody will be designed. (
  • Testing will be performed against a variety of cell lines expressing the target antigen. (
  • To improve the homogeneity, antigen-specificity and reduce possible autoreactivity, here we developed a technique to generate antigen-specific T cells from Rag2 gene-deleted pluripotent stem cells (PSCs) and further measured their anti-tumour efficacy. (
  • Our study presents a novel and straightforward strategy for producing antigen-specific TCR-T cells in vivo from PSCs, allowing for allogeneic transplantation and therapy of solid tumours. (
  • These lead to lysis of target cells and induction of specific cytokines (e.g., through NFAT, or nuclear factor activator of T-cells) in the effector cells. (
  • CD56 bright NK cells are known for their capacity to produce and secrete cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-γ, interleukin (IL)-10, IL-13, and TNF-β. (
  • A largely overlooked immune cell type in the context of immunotherapies are B cells, which can exert both anti-tumour and tumour-promoting effects by providing co-stimulatory signals and inhibitory signals for T cell activation, cytokines, and antibodies. (
  • Humanised immune system (HIS) mouse models that express human cytokines and support a broad range of human immune cell types have become integral tools to investigate and advance oncology drug discovery focused on cell-based therapies, which make up a growing proportion of cancer treatments. (
  • They also may express transgenic human cytokines to facilitate reconstitution and function of specific immune cell subsets needed to study cell therapy. (
  • Many studies have shown HIS and humanised transgenic models can support T cell functionality, with researchers using hIL2 transgenic models that express transgenic human IL2 (hIL2) cytokines to evaluate T cell therapies such as ACT/TIL,CAR-T, and TCR therapies. (
  • Use Incucyte ® live-cell imaging and analysis and iQue ® 3 advanced flow cytometry for activities such as immunophenotyping, assessment of functional activity, cell viability, immunophenotyping, and profiling of cytolytic effector proteins, cytokines, and chemokines. (
  • C) Additional cytokines were assessed in parallel by combining iQue ® Human NK Cell Companion Kits with the iQue ® Human NK Cell Killing Kit. (
  • Importantly, the OT1-iT cells eliminated tumour cells while releasing specific cytokines in vitro. (
  • Natural killer (NK) cells are part of the innate immune system and mediate responses against viruses, parasites, bacteria, and tumor cells. (
  • EOSINOPHILS Have granules that stain red with eosin Y. Mediate late phase of allergic response, active in immune response to parasites & tumors (antibodydependent cell-mediated cytotoxicity). (
  • After cell extension, the stably pMIG-infected cells had been isolated using stream cytometry analysis regarding to green fluorescent proteins expression. (
  • In mammalian cell based models of both polyglutamine and polyalanine diseases, the mutant proteins are much more prone to aggregate formation than their wild-type counterparts and cause significantly more cell death. (
  • This review summarizes some immunological factors involved in the development and control of this oral disease, such as: the participation of inflammatory cells in local inflammation, the synthesis of chemotaxis proteins with activation of the complement system and a range of antimicrobial peptides, such as defensins, cathelicidin and saposins. (
  • Non-Ab dependent or spontaneous lysis of cells increases background and decreases the dynamic antibody-specific signal range. (
  • Extra controls are required to subtract spontaneous lysis from both effector and target cells. (
  • The company showed that when performed in a 96-well plate, the percentage of target cell lysis is inversely proportional to the number of effector cells in each well. (
  • Merchant and colleagues also suggest that T-cell-depleting cancer therapies may eliminate beneficial immune responses and that immune reconstitution of patients with lymphopenic cancer could prevent metastatic recurrence of solid tumors. (
  • Thymomas, tumors that arise from epithelial cells of the thymus gland, are the most common neoplasms of the anterior mediastinum, with an incidence rate of approximately 2.5 per million/year. (
  • They are highly specific predators that play a major role in the host rejection of both tumors and viral infected cells. (
  • Recent studies revealed that nano-sized TiO2 can cause inflammatory response in airways of rats and mice, fibrosis or lung tumors in rats and DNA damage in Chinese hamster ovary (CHO) cells, Syrian hamster embryo fibroblasts and human lymphoblastoid cells. (
  • Basal cell carcinoma (BCC) is a malignant epithelial neoplasm and is the most common cancer in the head and neck region. (
  • Luminal SIgA is believed to interfere with pathogen adherence to mucosal epithelial cells, a process called immune exclusion. (
  • 2007. Inhibition of HIV-1 Infectivity and Epithelial Cell Transfer by Human Monoclonal IgG and IgA Antibodies Carrying the b12 V Region. (
  • Fate of airway epithelial cells exposed to titanium dioxide nanoparticles: NGF regulated apoptotic death. (
  • The primary human airway bronchial epithelial cells exposed to nanoparticles elicit high levels of neurotrophins, which has a significant role in modulating the cell cycle, cell proliferations and inflammatory responses. (
  • To evaluate the mechanism of TiO2 mediated toxicity, the bronchial epithelial cells were exposed to TiO2 (10 microg/mL) and the apoptosis and necrosis were measured. (
  • Epithelial-mesenchymal transition (EMT) and most cancers stem cells (CSCs) play a vital function in metastasis of papillary thyroid most cancers (PTC). (
  • Materials and Methods Cell Culture and RNA Extraction Two subclones of W12 cervical epithelial cells with HPV16 in differing physical states were a gift from Dr. Paul Lambert (University of Wisconsin, Madison, WI). (
  • In conclusion, C5a induces the formation of NETs from PMN-MDSCs in the presence of cancer cells, which may facilitate cancer cell dissemination and metastasis. (
  • mAb 2C7 causes complement (C')-dependent bacteriolysis of three (2-Hex/G+, 4-Hex/G+, and 5-Hex/G+) of the HepI mutants in vitro. (
  • The engineered PSCs were then differentiated through a two-step strategy, in vitro generation of haematopoietic progenitor cells, and in vivo development and maturation of TCR-T cells. (
  • Finally, the response to tumour cells was assessed in vitro and in vivo. (
  • Additional reported applications (for the relevant formats) include: immunoprecipitation 1-3 , complement-dependent cytotoxicity 4 , in vivo and in vitro blocking of adhesion 1-3,5 , and immunohistochemical staining of acetone-fixed frozen sections and zinc-fixed paraffin-embedded sections 6 . (
  • in vitro, and on the other hand, HHT causes raised ROS era in ETP-treated AML cells. (
  • It demonstrated satisfactory preclinical safety profiles based on evaluations of in vitro cytotoxicity, skin sensitization, intracutaneous reactivity, and systemic toxicity. (
  • The released MMAF intracellularly disrupts the microtubule network, leading to cell cycle arrest and apoptosis. (
  • Perforins form pores in the cell membrane of the target cell through which the granzymes and associated molecules induce apoptosis. (
  • The Protein kinase C (PKC) -associated sign pathway performs essential roles in regulation of cell development, differentiation and apoptosis. (
  • a minority of the cells (10%) are CD56 bright and CD16 dim/neg . (
  • E,F) Detection of CD16 on NK cells decreased with increasing concentration of anti-CD20 antibody. (
  • This could be due to CD16 shedding or competition of CD20 antibody. (
  • Regarding CD16-158V/F polymorphism, the antibody 3G8 detects both 158V and 158F allotype on natural NK cells. (
  • Since some of the NSAbs interfere with neurotransmission pathways related to depression ( 26 - 28 ), a subtype of depression may be caused by antibody-mediated autoimmunity and, therefore, might potentially respond to immunotherapy. (
  • Schematic representation of IL-21 signaling pathways and its main biological effects on different target cells. (
  • 10, 11 In such models, aggregate formation and cell death can be reduced by overexpressing yeast and bacteria derived chaperones that do not appear to protect against some other cell death pathways. (
  • During reprogramming, somatic cells endure dramatic modifications in a wide selection of mobile processes, equivalent to metabolism, mitochondrial morphology and performance, cell signaling pathways or immortalization . (
  • Several preclinical studies showed that IL-21 has antitumor activity in different tumor models, through mechanism involving the activation of NK and T or B cell responses. (
  • Immunotherapies have become more popular due to their ability to trigger and train the patient's immune system to recognise and attack tumour cells, provide strong immune responses, and reduce the severity of adverse side effects generally associated with chemotherapies. (
  • Innate lymphoid cells (ILCs) play important roles in regulating tissue homeostasis and innate immune responses. (
  • In this study, we found that coffee extract at more than 2.5%(v/v) significantly inhibited LPS-induced inflammatory responses in RAW264.7 cells and that anti-inflammatory activity of coffee required the roasting process. (
  • Gicobi JK, Dellacecca ER, Dong H . Resilient T-cell responses in patients with advanced cancers. (
  • CONCLUSIONS These findings imply that LC produced increased neutralizing antibody responses than those with HC. (
  • Here, we find that B cells significantly enhance primary CD8 T cell responses after vaccination. (
  • We also show that interleukin-27 production by B cells contributes to their impact on primary, but not memory, CD8 responses. (
  • Mast cell FcgammaRIII-A is associated, moreover, with FcepsilonRI-beta subunit. (
  • BASOPHILS AND MAST CELLS Have basophilic granules, stain bluish black with basic dyes. (
  • Basophils circulate, mast cells found in tissue. (
  • Mast cells: BM derived cells, differentiate in blood and connective tissue. (
  • bound to the surface of mast cells. (
  • The results showed that the dense lymphocytic infiltrate surrounding neoplastic cells of BCC consisted chiefly of T-lymphocytes. (
  • Stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production. (
  • Natural killer cells, also known as NK cells are a type of lymphocytes and are key components of the innate immune system. (
  • NK cells are derived from the common lymphoid progenitor cells (lymphoblasts), which also generate B and T lymphocytes. (
  • The greatest province of these APCs is to mete out these peptide-MHC complexes to T-lymphocytes (T-cells), an impor- tant component of the adaptive untouched system. (
  • Understanding the response of tumor cells to antibodies with Fc-dependent MoA has the potential to improve the efficacy of antibody therapeutics and identify rational combination partners. (
  • FcγRIIIa polymorphism of individual cancer patients are correlated with clinical efficacy of some of these antibody drugs. (
  • Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study. (
  • Partial efficacy of a broadly neutralizing antibody against cell-associated SHIV infection. (
  • Broadly neutralizing antibodies (BnAbs) protect macaques from cell-free simian/human immunodeficiency virus (SHIV) challenge, but their efficacy against cell-associated SHIV is unclear. (
  • Our results show that HIV-1-specific neutralizing antibodies have partial efficacy against cell-associated virus exposure in macaques. (
  • Resveratrol (Res) exerts inhibitory effects on breast cancer cell lines and animal models, while its efficacy against individual breast cancer cases remains unknown. (
  • Using a variety of syngenic and xenograft models, we demonstrate here that the inhibitory FcgammaRIIB molecule is a potent regulator of antibody-dependent cell-mediated cytotoxicity in vivo, modulating the activity of FcgammaRIII on effector cells. (
  • In vivo models, particularly HIS models, allow preliminary investigation of cell-based therapeutic strategies-often in combination with other therapeutic modalities-to overcome the limitations and challenges of T cell-based immuno-oncology treatments and identify effective options for clinical investigation. (
  • In vivo data confirmed that ALKBH5 upregulated UBE2C expression by regulating the m6A modification of UBE2C and reduced p53 expression, thus promoting the stemness, growth and metastasis of TNBC cells. (
  • While WA/1 virus exhibited a moderately increased proportion compared to that in the inoculum following co-infection in human respiratory cells, Delta variant possessed a substantial in vivo fitness advantage as this virus becoming predominant in both inoculated and contact animals. (
  • Single-cell transcriptomics illustrates the developmental trajectory of PSC-derived ILCs in vivo, which is consistent with that of natural ILCs. (
  • 11, 15 Members of the HSP70 and HSP40 family members are recruited to polyQ inclusions in vivo and in cell models. (
  • In addition, beagle canine PBMCs are used in ex-vivo applications, such as cell population characterization based on immunophenotyping. (
  • Direct and antibody dependent cell mediated cytotoxicity against Giardia lamblia by splenic and intestinal lymphoid cells in mice. (
  • It is important to quantify the biological activity of any therapeutic antibody in a bioassay during drug development and manufacture. (
  • To mitigate these risks, clinicians are turning to other immunomodulators, such as cell-based therapies, bispecific antibodies, and cytokine treatments. (
  • Cytokine stimulation enhances direct NK cell-mediated killing of tumor cells. (
  • A) Histogram depicting target cell viability following co-culture with non-activated or cytokine activated NK cells for 4 h. (
  • B,C) Summary of percent target cell death following co-culture of tumor cells with non-activated or cytokine activated NK cells for (B) 4 h or (C) 24 h. (
  • NK cell activation is induced in the presence of target cells and further enhanced by cytokine stimulation. (
  • TNFSF14 can be a cytokine neutralization target during novel coronavirus infection, and anti-TNFSF14 monoclonal antibody treatment can reduce the risk of respiratory failure and mortality. (
  • Elevation of IL-10 levels in NK cells and reduction of CD3+ and CD8+ T cells in severe patients might be considered as a protective response against the harmful effect of cytokine storm seen in COVID-19. (
  • Moreover, memory CD8 numbers and function are impaired in B-cell-deficient animals, leading to increased susceptibility to bacterial challenge. (
  • 15e has been shown to recognize a conformation-dependent epitope on gp120 which is important in both CD4 binding and neutralizing of HIV-1 infection. (
  • The mutation in VZV-MSP led to a lost B-cell epitope in of enveloped virus characteristic of herpesviruses. (
  • Both VZV-MSP and VZV-BC pox and was admitted to hospital for treatment with intrave- are escape mutants (i.e., they have lost a B-cell epitope present nous acyclovir. (
  • Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy. (
  • Helps maintain human pluripotent stem cells in undifferentiated state. (
  • Origination - pluripotent stem cells (fetal liver & bone marrow of animal host) Pluripotent- not yet committed to differentiate. (
  • Regenerating prolonged multi-lineage hematopoiesis from pluripotent stem cells (PSCs), an unlimited cell source, is a crucial aim of regenerative hematology. (
  • Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells. (
  • This results in a high level of expression of the fusion protein inside the target cells. (
  • The KILR Retroparticles for Suspension cells contain a hybrid LTR promoter for expression of the fusion protein in difficult-to-transduce suspension cell lines, whereas the KILR Retroparticles for Adherent cells use a CMV promoter for expression of the KILR construct in most adherent cell lines. (
  • Death of the cells leads to rupture of the cell membrane and the KILR reporter protein is released into the medium. (
  • Therapeutic antibodies are now the major class of successful protein drugs with many more in development to target a variety of major diseases. (
  • TotalSeq™-D antibodies are compatible with Mission Bio's Tapestri Single-Cell Sequencing Platform for simultaneous detection of DNA and Protein. (
  • TotalSeq™-D reagents are designed to profile protein expression at single cell level. (
  • NASDAQ:MOR), and Incyte (NASDAQ:INCY) today announced a clinical trial collaboration and supply agreement to investigate the immunotherapeutic combination of Pfizer's TTI-622, a novel SIRPα-Fc fusion protein, and Monjuvi® (tafasitamab-cxix) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT). (
  • Activation of cAMP-dependent protein kinase is required for heterologous desensitization of adenylyl cyclase in S49 wild-type lymphoma cells. (
  • Purified antibody is conjugated with activated tandem dye of activated Peridinin-Chlorophyll Protein-Cyanine 5.5 (PerCP-Cy™5.5) under optimum conditions and unconjugated antibody and free fluorochrome are removed by size-exclusion chromatography. (
  • Human FcgammaRIII is expressed in two forms - FcgammaRIII-A and -B. FcgammaRIII-A is a transmembrane protein of monocytes, macrophages, NK cells and a subset of T cells. (
  • third, the GAPDH-Siah protein complex translocates to the nucleus, dependent on Siah1's nuclear localization signal, and degrades Siah1's substrates in the nucleus, which results in cytotoxicity. (
  • Differentiation-Associated Expression of Conventional Protein Kinase C Isoforms in Primary Cultures of Bone Marrow Cells Induced by M-CSF and G-CSF. (
  • We sought to find out the protein content material in serum exosomes (SEs), to characterise SEs, and to find novel scientific biomarkers of oral squamous cell carcinoma (OSCC). (
  • 1 Nevertheless, strategies that target protein misfolding frequently reduce aggregate formation and cell death in parallel. (
  • 11, 14 Rouleau and colleagues found that oligomerisation of PABP2 is mediated by two potential oligomerisation domains (ODs)-deletions in either of these domains inactivated oligomerisation of mutant PABP2 and also reduced the cell death caused by this protein. (
  • Figure 3: Co-stimulatory and co-inhibitory molecules set thresholds for T-cell activation. (
  • A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages. (
  • It is expressed on the surface of NK cells, activated monocytes, macrophages, and placental trophoblasts in humans. (
  • It is a member of the selectin family and is expressed on the majority of B and naïve T cells, a subset of memory T cells, monocytes, granulocytes, most thymocytes, and a subset of NK cells. (
  • Over 100+ NK Cell Therapy companies are evaluating 185+ NK Cell Therapy therapies in various stages of development, and their anticipated acceptance in the NK Cell Therapy market would significantly increase market revenue. (
  • The NK Cell Therapy Companies and academics are working to assess challenges and seek opportunities that could influence Natural Killer (NK) cell therapy R&D. The NK Cell Therapy pipeline therapies under development are focused on novel approaches to treat/improve Natural Killer (NK) cell therapy. (
  • Myeloid-derived suppressor cells (MDSCs) play a major role in cancer progression. (
  • The iHPCs engrafted successfully in wild-type animals and repopulated abundant and complete myeloid-, B-, and T-lineage mature cells. (
  • Transcriptome characterization of generative myeloid, B, and T cells at the single-cell resolution further projected their identities to natural cell counterparts. (
  • Thus, we provide evidence that co-expression of exogenous Runx1, Hoxa9, and Hoxa10 simultaneously leads to long-term reconstitution of myeloid, B, and T lineages using PSC-derived iHPCs as the cell source. (
  • Background/Aims Cytotoxicity induced by reactive air species (ROS) is crucial for the potency of chemotherapeutic medications used in the treating acute myeloid leukemia (AML). (
  • The current research focuses on typical PKC (cPKC) expression and its regulation in major cultures of bone marrow cells induced to endure macrophage/granulocyte differentiation by macrophage colony-stimulating issue (M-CSF) or granular colony-stimulating issue (G-CSF). (
  • The relationship between B cells and CD4 T cells has been carefully studied, revealing a collaborative effort in which B cells promote the activation, differentiation, and expansion of CD4 T cells while the so-called "helper" cells provide signals to B cells, influencing their class switching and fate. (
  • Finally, beagle canine PBMCs are a good source of cells to test cross-reactivity of test molecules across a range of animals. (
  • As a proof of concept, we used FlowCT to compare the T-cell compartment in bone marrow (BM) with peripheral blood (PB) from patients with smoldering multiple myeloma (SMM), identify minimally invasive immune biomarkers of progression from smoldering to active MM, define prognostic T-cell subsets in the BM of patients with active MM after treatment intensification, and assess the longitudinal effect of maintenance therapy in BM T cells. (
  • 3086432 ). These NK cell subsets lack CD3 expression and are phenotypically and functionally distinct. (
  • Additional NK cell subsets can be identified according to their tissue distribution. (
  • The 3-Hex/G+ mutant (resistant to C'-dependent bacteriolysis) is killed by neutrophils in the presence of mAb and C'. In mice, 2- and 3-Hex/G+ infections are significantly shorter than 4- and 5-Hex/G+ infections. (
  • GRANULOCYTES Polymorphonuclear leukocytes (PMNs) Neutrophils: Predominant type of white blood cell. (
  • Binding of both proteinase 3 (PR3) and myeloperoxidase (MPG) to endothelial cells (EC) has been suggested to be involved in the vascular damage seen in patients with Wegener's granulomatosis or microscopic polyangiitis. (
  • In the present study we investigated in detail the interaction of MPO and PR3 with cultured human umbilical vein endothelial cells (HUVEC) and its matrix products. (
  • Detailed analysis of the binding of PR3 to HUVEC monolayers showed that PR3 binds primarily to the extracellular matrix of endothelial cells, and to a very limited extent to the cells themselves. (
  • For MPO it was shown that it binds both to the extracellular matrix and to the endothelial cells themselves. (
  • Scientists started envisioning using monoclonal antibody (mAbs, for short) against HIV almost a quarter of a century ago. (
  • IgA MAbs can hardly be obtained through the classical hybridoma technique that involves the fusion between murine splenocytes and myeloma cells [7] . (
  • In this regard, we are using an innovative method to generate IgA MAbs which combines hybridoma and recombinant DNA technologies to produce IgA in CHO cells. (
  • Increasing evidence of the clinical translatability of HIS mouse models is proving essential to advancing cell-based immunotherapies that may overcome the challenges of first-generation immuno-oncology therapeutics. (
  • It also covers the NK Cell Therapy pipeline therapeutics assessment by product type, stage, route of administration, and molecule type. (
  • Antibodies with 15e-like activity may be useful in immunoprophylaxis or immunotherapy of HIV-1 infection. (
  • Two methods for measuring the activity of antibody-dependent cell-mediated cytotoxicity are compared. (
  • Binding of PR3 to HUVEC cultures (cells + matrix) was inhibited by fetal calf serum and by α 1 -antitrypsin, but inactivation of enzymatic activity of PR3 by PMSF did not influence binding of PR3 to HUVEC cultures. (
  • Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. (
  • Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: Results from the phase Ib KEYNOTE-012 expansion cohort. (
  • 11 CaSki, a human cervical cancer cell collection, was obtained from American Type INCB018424 biological activity Culture Collection (Manassas, VA). CaSki monolayers were grown in RPMI-1640 medium with 10% FBS and 2.5 mmol/L L-glutamine. (
  • De Souza CEA, Andrade Pires AR, Cardoso CR, Carlos RM, Cadena SMSC, Acco A (2020) Antineoplastic activity of a novel ruthenium complex against human hepatocellular carcinoma (HepG2) and human cervical adenocarcinoma (HeLa) cells. (
  • Depending on the species (human or non-human) of blood, either 1.077 or 1.084 g/ml Ficoll is used, resulting in a perfect layer of mononuclear cells that are separated from plasma, platelets, granulocytes, and erythrocytes. (
  • The cells that have the inherent property of innate and adaptive immunity within the body are present at different sites including the blood, lymphatic system (lymph, lymphoid nodules and lymphoid organs), epithelium, and connective tissues. (
  • It could be of importance to identify the immunologically competent cells among the mononuclear cell infiltration as they might signify an immunological reaction around the tumour. (
  • Furthermore, adoptive transfer of OT1-iT cells suppresses solid tumour growth in tumour-bearing animals. (
  • Blood exosomes assist regulate communication between tumour cells, moderating their behaviour. (
  • Since the pioneering attempts of Denekamp and colleagues in the mid-1970s to sensitize hypoxic tumour cells (Fowler et al. (
  • Most patients exhibit neutrophil-predominant airway inflammation combined with an increase in macrophages and CD8 + T-cells. (
  • The antibody was purified by chromatography and conjugated with TotalSeq™-D oligomer under optimal conditions. (
  • To evaluate whether a BnAb can prevent infection after cell-associated viral challenge, we infused pigtail macaques with PGT121 or an isotype control and challenged animals 1 hour later intravenously with SHIVSF162P3-infected splenocytes. (