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.
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.
Antibodies produced by a single clone of cells.
Immunoglobulins produced in response to VIRAL ANTIGENS.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
A form of antibodies consisting only of the variable regions of the heavy and light chains (FV FRAGMENTS), connected by a small linker peptide. They are less immunogenic than complete immunoglobulin and thus have potential therapeutic use.
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.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.
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.
Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques.
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.
Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.
Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.
Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
Sites on an antigen that interact with specific antibodies.
Antibodies reactive with HIV ANTIGENS.
Immunoglobulins produced in a response to PROTOZOAN ANTIGENS.
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.
Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.
Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.
Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.
Use of radiolabeled antibodies for diagnostic imaging of neoplasms. Antitumor antibodies are labeled with diverse radionuclides including iodine-131, iodine-123, indium-111, or technetium-99m and injected into the patient. Images are obtained by a scintillation camera.
Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.
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.
Semisynthetic conjugates of various toxic molecules, including RADIOACTIVE ISOTOPES and bacterial or plant toxins, with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; and ANTIGENS. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect.
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).
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
An iron chelating agent with properties like EDETIC ACID. DTPA has also been used as a chelator for other metals, such as plutonium.
Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.
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.
Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.
A lectin and cell adhesion molecule found in B-LYMPHOCYTES. It interacts with SIALIC ACIDS and mediates signaling from B-CELL ANTIGEN RECEPTORS.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Immunoglobulins produced in a response to FUNGAL ANTIGENS.
A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.
An immunoglobulin fragment composed of one variable domain from an IMMUNOGLOBULIN HEAVY CHAIN or IMMUNOGLOBULIN LIGHT CHAIN.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.
The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).
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.
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.
Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.
Unstable isotopes of indium that decay or disintegrate emitting radiation. In atoms with atomic weights 106-112, 113m, 114, and 116-124 are radioactive indium isotopes.
Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Proteins prepared by recombinant DNA technology.
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.
Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).
Established cell cultures that have the potential to propagate indefinitely.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Antibodies elicited in a different species from which the antigen originated. These antibodies are directed against a wide variety of interspecies-specific antigens, the best known of which are Forssman, Hanganutziu-Deicher (H-D), and Paul-Bunnell (P-B). Incidence of antibodies to these antigens--i.e., the phenomenon of heterophile antibody response--is useful in the serodiagnosis, pathogenesis, and prognosis of infection and latent infectious states as well as in cancer classification.
Antibodies that can catalyze a wide variety of chemical reactions. They are characterized by high substrate specificity and share many mechanistic features with enzymes.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A cell line derived from cultured tumor 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.
Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.
Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.
Substances that are recognized by the immune system and induce an immune reaction.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
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 class of organic compounds containing a ring structure made up of more than one kind of atom, usually carbon plus another atom. The ring structure can be aromatic or nonaromatic.
Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.
A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.
Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.
Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC;), ANTIPHOSPHOLIPID SYNDROME; related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals.
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.
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.
The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.
Transplantation between animals of different species.
Substances elaborated by bacteria that have antigenic activity.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A technique using antibodies for identifying or quantifying a substance. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance.
Elements of limited time intervals, contributing to particular results or situations.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
Anti-CD3 monoclonal antibody that exerts immunosuppressive effects by inducing peripheral T-cell depletion and modulation of the T-cell receptor complex (CD3/Ti).
Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.
The sum of the weight of all the atoms in a molecule.
Antibodies obtained from a single clone of cells grown in mice or rats.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
Substances elaborated by viruses that have antigenic activity.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers.
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.
Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Sensitive tests to measure certain antigens, antibodies, or viruses, using their ability to agglutinate certain erythrocytes. (From Stedman, 26th ed)
Serologic tests in which a known quantity of antigen is added to the serum prior to the addition of a red cell suspension. Reaction result is expressed as the smallest amount of antigen which causes complete inhibition of hemagglutination.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Autoantibodies directed against cytoplasmic constituents of POLYMORPHONUCLEAR LEUKOCYTES and/or MONOCYTES. They are used as specific markers for GRANULOMATOSIS WITH POLYANGIITIS and other diseases, though their pathophysiological role is not clear. ANCA are routinely detected by indirect immunofluorescence with three different patterns: c-ANCA (cytoplasmic), p-ANCA (perinuclear), and atypical ANCA.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
EPIDEMIOLOGIC STUDIES based on the detection through serological testing of characteristic change in the serum level of specific ANTIBODIES. Latent subclinical infections and carrier states can thus be detected in addition to clinically overt cases.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains.
Techniques used to demonstrate or measure an immune response, and to identify or measure antigens using antibodies.
A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.
Ribosome inactivating proteins consisting of only the toxic A subunit, which is a polypeptide of around 30 kDa.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.
Cytolytic lymphocytes with the unique capacity of killing natural killer (NK)-resistant fresh tumor cells. They are INTERLEUKIN-2-activated NK cells that have no MAJOR HISTOCOMPATIBILITY COMPLEX restriction or need for antigen stimulation. LAK cells are used for ADOPTIVE IMMUNOTHERAPY in cancer patients.
Hoofed mammals with four legs, a big-lipped snout, and a humped back belonging to the family Camelidae.
An encapsulated lymphatic organ through which venous blood filters.
The rate dynamics in chemical or physical systems.

Immunotherapy of human tumors with T-cell-activating bispecific antibodies: stimulation of cytotoxic pathways in vivo. (1/429)

Bispecific monoclonal antibodies (Bi-mAbs) specific for a tumor-associated antigen and the CD3 or CD28 antigen on T lymphocytes represent one of the most successful experimental strategies for the immunotherapy of cancer. We report that the in vivo administration of both alpha-CD3/CD30 and alpha-CD28/CD30 Bi-mAbs results in the specific activation of xenotransplanted, resting human T cells infiltrating the CD30-positive Hodgkin's tumor. Bi-mAb treatment resulted in enhanced expression of cytokines such as interleukin 1beta, interleukin 2, tumor necrosis factor type alpha, and activation markers including Ki-67, CD25, and CD45RO in tumor-infiltrating lymphocytes. This antigen-dependent, local T-cell stimulation led to the activation of the cytolytic machinery in T lymphocytes, determined by the up-regulation of mRNA-encoding perforin and the cytotoxic serine-esterases granzymes A and B. The Bi-mAb-induced generation of CTLs depended on the presence of the CD30 antigen and the combined application of both Bi-mAbs. Our findings suggest that the combined application of T-cell-activating Bi-mAbs is able to achieve a tumor site-specific activation of the T-cell cytolytic machinery in vivo. The fact that these cytotoxic cells do not home in tumor-associated antigen-negative tissue and do not enter circulation might explain our previous observations (C. Renner et al., Blood, 87: 2930-2937, 1996) of a high cure rate in preclinical models even at an advanced stage of disease.  (+info)

Dual specificity antibodies using a double-stranded oligonucleotide bridge. (2/429)

The covalent conjugation of oligonucleotides to antibody Fab' fragments was optimized by using oligonucleotides modified with a hexaethylene linker arm bearing three amino groups. One oligonucleotide was coupled to antibody of one specificity and a complementary oligonucleotide to antibody of a second specificity. The antibodies were then allowed to hybridize by base pairing of the complementary nucleotide sequences and the generation of bispecific antibody was analyzed on SDS-PAGE and confirmed using BIAcore analysis. The strategy of complementary oligonucleotide-linked bispecific molecules is not limited to antibodies but is applicable to linking any two molecules of different characteristics.  (+info)

An effective strategy of human tumor vaccine modification by coupling bispecific costimulatory molecules. (3/429)

A new, generally applicable procedure is described for the introduction of defined costimulatory molecules into human cancer cells to increase their T-cell stimulatory capacity. The procedure involves infection with Newcastle disease virus to mediate the cell surface binding of costimulatory molecules (e.g., specially designed bispecific antibodies (bsAb)). The modification is independent of tumor cell proliferation and laborious recombinant gene technology and can be applied directly to freshly isolated and gamma-irradiated patient-derived tumor cells as an autologous cancer vaccine. Following the infection of tumor cells with a nonvirulent strain of Newcastle disease virus, the cells are washed and then further modified by coincubation with bsAbs, which attach with one arm to the viral hemagglutinin-neuraminidase (HN) molecule on the infected tumor cells. The second specificity of one bsAb (bs HN x CD28) is directed against CD28 to augment antitumor T-cell responses by selectively channeling positive costimulatory signals via the CD28 pathway. A second bsAb (bs HN x CD3) was produced to deliver T-cell receptor-mediated signals either alone (bsCD3 vaccine) or in combination with anti-CD28 (bsCD3 vaccine plus bsCD28 vaccine). In human T-cell stimulation studies in vitro, the bsCD28 vaccine caused an up-regulation of early (CD69) and late (CD25) T-cell activation markers on CD4 and CD8 T lymphocytes from either normal healthy donors or cancer patients (autologous system) and induced tumor cytostasis in nonmodified bystander tumor cells. In addition, in combination with the bsCD3 vaccine, augmented antitumor cytotoxicity and T-cell proliferative responses were observed. This tumor vaccine modification procedure is highly specific, quick, economic, and has a broad range of clinical applications.  (+info)

Carcinoembryonic antigen (CEA)-specific T-cell activation in colon carcinoma induced by anti-CD3 x anti-CEA bispecific diabodies and B7 x anti-CEA bispecific fusion proteins. (4/429)

Two bispecific recombinant molecules, an anti-CD3 x anti-carcinoembryogenic antigen (CEA) diabody and a B7 x anti-CEA fusion protein, were tested for their capacity to specifically activate T cells in the presence of CEA-expressing colon carcinoma cells. T-cell activation by the anti-CD3 x anti-CEA diabody required close contact to CEA-positive cells and resulted in diabody-mediated cytotoxicity against the target cells. Additionally, CD28-mediated costimulation in combination with anti-CD3 x anti-CEA diabodies induced activation of autologous T cells in CEA-positive primary colon carcinoma specimens, as determined by flow cytometry. The high specificity of the bispecific diabody approach could be further enhanced by the use of B7 x anti-CEA fusion proteins because the costimulatory CD28-signaling to the T cells strictly depended on the expression of CEA on the target cells. We demonstrate that displaying engagement sites for the T-cell antigens CD3 and CD28 on the surface of colon carcinoma cells is a suitable way to activate and retarget T cells in a highly tumor-specific manner. For clinical purposes, B7 x anti-tumor-associated antigen (TAA) fusion proteins, which are equally effective but more specific compared with anti-CD28 monoclonal anti-bodies, thus may improve the tumor specificity of anti-CD3 x anti-TAA bispecific antibodies. Furthermore, B7-negative tumors can be converted into B7-positive tumors by B7 x anti-TAA fusion proteins without the need for B7 gene transfer to the malignant cells.  (+info)

Two-step targeting and dosimetry for small cell lung cancer xenograft with anti-NCAM/antihistamine bispecific antibody and radioiodinated bivalent hapten. (5/429)

The "affinity enhancement system," a two-step targeting technique using bispecific antibody and radiolabeled bivalent hapten, has been reported to be useful for carcinoembryonic antigen-expressing tumors. The purpose of this study was to evaluate the efficacy of this method for targeting human small cell lung cancer using an antineural cell adhesion molecule antibody. METHODS: Antineural cell adhesion molecule/antihistamine bispecific antibody NK1NBL1-679 was prepared by coupling an equimolecular quantity of a Fab' fragment of NK1NBL1 to a Fab fragment of antihistamine 679. Athymic mice inoculated with NCI-H69 small cell lung cancer cells expressing neural cell adhesion molecule were administered bispecific antibody and then 48 h later 125I-labeled bivalent histamine hapten. 125I-labeled intact NK1NBL1 was injected into other groups of mice. Biodistributions were examined as a function of time. RESULTS: In mice of the two-step targeting, tumor uptake was 2.5 +/- 0.2, 3.2 +/- 0.4, 6.4 +/- 2.0, 7.2 +/- 2.7, 6.1 +/- 2.1 and 2.2 +/- 0.4 %ID/g at 5, 30 min, 5, 24, 48 and 96 h, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 1.4 +/- 1.1, 10.8 +/- 13.2 and 4.6 +/- 4.7, respectively, at 5 h, whereas 125I-labeled NK1NBL1 showed a tumor uptake of 5.7 +/- 0.4 %ID/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 0.3 +/- 0.1, 1.1 +/- 0.2 and 0.9 +/- 0.1, respectively, at 5 h. These results were confirmed by autoradiographic studies, which demonstrated clear tumor-to-normal tissue contrast. Dosimetry showed that the affinity enhancement system could enhance the therapeutic potential of the antineural cell adhesion molecule antibody NK1NBL1. CONCLUSION: This two-step targeting method seems promising for the diagnosis and therapy of small cell lung cancer.  (+info)

Expression and characterization of bispecific single-chain Fv fragments produced in transgenic plants. (6/429)

We describe the expression of the bispecific antibody biscFv2429 in transgenic suspension culture cells and tobacco plants. biscFv2429 consists of two single-chain antibodies, scFv24 and scFv29, connected by the Trichoderma reesi cellobiohydrolase I linker. biscFv2429 binds two epitopes of tobacco mosaic virus (TMV): the scFv24 domain recognizes neotopes of intact virions, and the scFv29 domain recognizes a cryptotope of the TMV coat protein monomer. biscFv2429 was functionally expressed either in the cytosol (biscFv2429-cyt) or targeted to the apoplast using a murine leader peptide sequence (biscFv2429-apoplast). A third construct contained the C-terminal KDEL sequence for retention in the ER (biscFv2429-KDEL). Levels of cytoplasmic biscFv2429 expression levels were low. The highest levels of antibody expression were for apoplast-targeted biscFv2429-apoplast and ER-retained biscFv2429-KDEL that reached a maximum expression level of 1.65% total soluble protein in transgenic plants. Plant-expressed biscFv2429 retained both epitope specificities, and bispecificity and bivalency were confirmed by ELISA and surface plasmon resonance analysis. This study establishes plant cells as an expression system for bispecific single-chain antibodies for use in medical and biological applications.  (+info)

Novel tetravalent and bispecific IgG-like antibody molecules combining single-chain diabodies with the immunoglobulin gamma1 Fc or CH3 region. (7/429)

Although bispecific IgG molecules have been successfully applied for antibody-mediated immunotherapy of tumours, applicability is hampered by the difficulties associated with their generation. In the present study, we have used a bispecific single-chain diabody (scDb) directed against carcinoembryonic antigen and Escherichia coli beta-galactosidase as a model to generate bispecific IgG-like antibody molecules. We show that the fusion of this single-chain diabody to the Fc (scDb-Fc) or CH3 (scDb-CH3) region of the human immunoglobulin gamma1 chain results in the expression of dimeric fusion proteins exhibiting four functional antigen binding sites with increased functional affinity. This strategy represents a new and convenient way to generate IgG-like multivalent and bispecific molecules that are efficiently secreted from mammalian cells.  (+info)

Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing. (8/429)

Bispecific Abs (bsAb) are promising immunological tools for the elimination of tumor cells in minimal residual disease situations. In principle, they target an Ag on tumor cells and recruit one class of effector cell. Because immune reactions in vivo are more complex and are mediated by different classes of effector cell, we argue that conventional bsAb might not yield optimal immune responses at the tumor site. We therefore constructed a bsAb that combines the two potent effector subclasses mouse IgG2a and rat IgG2b. This bispecific molecule not only recruits T cells via its one binding arm, but simultaneously activates FcgammaR+ accessory cells via its Fc region. We demonstrate here that the activation of both T lymphocytes and accessory cells leads to production of immunomodulating cytokines like IL-1beta, IL-2, IL-6, IL-12, and DC-CK1. Thus this new class of bsAb elicits excellent antitumor activity in vitro even without the addition of exogenous IL-2, and therefore represents a totally self-supporting system.  (+info)

With the development of molecular cloning technology and the deep understanding of antibody engineering, there are diverse bispecific antibody formats from which to choose to pursue the optimal biological activity and clinical purpose. The single-chain-based bispecific antibodies usually bridge tumor cells with immune cells and form an immunological synapse because of their relatively small size. Bispecific antibodies in the IgG format include asymmetric bispecific antibodies and homodimerized bispecific antibodies, all of which have an extended blood half-life and their own crystalline fragment (Fc)-mediated functions. Besides retargeting effector cells to the site of cancer, new applications were established for bispecific antibodies. Bispecific antibodies that can simultaneously bind to cell surface antigens and payloads are a very ideal delivery system for therapeutic use. Bispecific antibodies that can inhibit two correlated signaling molecules at the same time can be developed to overcome inherent
A trifunctional antibody is a monoclonal antibody with binding sites for two different antigens, typically CD3 and a tumor antigen, making it a type of bispecific monoclonal antibody. In addition, its intact Fc-part can bind to an Fc receptor on accessory cells like conventional monospecific antibodies. The net effect is that this type of drug links T cells (via CD3) and monocytes/macrophages, natural killer cells, dendritic cells or other Fc receptor expressing cells to the tumor cells, leading to their destruction. At an equivalent dose a trifunctional antibody is more potent (more than 1,000-fold) in eliminating tumor cells than conventional antibodies. These drugs evoke the removal of tumor cells by means of (i) antibody-dependent cell-mediated cytoxicity, a process also described for conventional antibodies and more importantly by (ii) polyclonal cytotoxic T cell responses with emphasis on CD8 T cells. These trifunctional antibodies also elicit individual anti-tumor immune responses in ...
TRION Pharma Release: Trifunctional Antibody Catumaxomab Triggers Vaccination Effect Against Cancer - read this article along with other careers information, tips and advice on BioSpace
TY - JOUR. T1 - In vitro selection of bispecific diabody fragments using covalent bicistronic DNA display. AU - Nakayama, Masanao. AU - Komiya, Shoko. AU - Fujiwara, Kei. AU - Horisawa, Kenichi. AU - Doi, Nobuhide. N1 - Funding Information: We thank Takeshi Sumida and Hiroshi Yanagawa for early contributions to this project. This research was supported in part by a Grant-in-Aid for Scientific Research ( 19360377 , 22360351 , 25289298 , 15K12545 , 15H01543 and 16H05291 ) from the JSPS or MEXT of Japan, by the Mochida Memorial Foundation for Medical and Pharmaceutical Research , and by the Strategic Research Foundation Grant-aided Project for Private Universities ( S1411003 ) from the MEXT of Japan. Publisher Copyright: © 2016 Elsevier Inc.. PY - 2016/9/16. Y1 - 2016/9/16. N2 - Bispecific antibodies with two different antigen-binding sites have been widely used for a variety of medical applications. The activity and stability of antibody fragments can be improved by in vitro evolution. Although ...
Bispecific antibodies (bsAbs) participating T cells are rising as a probable immunotherapeutic tool for the treatment of hematologic malignancies. co-stimulus buy AescinIIB via the Compact disc137-Compact disc137 ligand axis through Compact disc137L reflection on MSCs. This research demonstrates that MSCs possess the potential to end up being utilized buy AescinIIB as mobile creation devices for bsAb-based growth immunotherapy in the potential. Launch T-cell getting bispecific antibodies (bsAbs) are a appealing device for cancers treatment. This course of antibodies creates a transient synapse between Testosterone levels cells and cancers cells by presenting to a surface area antigen on cancers cells with one limb and concurrently enrolling Testosterone levels cells via the Compact disc3 domains, which is normally the indication sending part of the T-cell receptor complicated.1 The polarization of the T-cell complicated network marketing leads to an activation of bsAb buy AescinIIB recruited T ...
Oncolytic viruses exploit the cancer cell phenotype to complete their lytic life cycle, releasing progeny virus to infect nearby cells and repeat the process. We modified the oncolytic group B adenovirus EnAdenotucirev (EnAd) to express a bispecific single-chain antibody, secreted from infected tumour cells into the microenvironment. This bispecific T-cell engager (BiTE) binds to EpCAM on target cells and cross-links them to CD3 on T cells, leading to clustering and activation of both CD4 and CD8 T cells. BiTE transcription can be controlled by the virus major late promoter, limiting expression to cancer cells that are permissive for virus replication. This approach can potentiate the cytotoxicity of EnAd, and we demonstrate using primary pleural effusions and peritoneal malignant ascites that infection of cancer cells with the BiTE-expressing EnAd leads to activation of endogenous T cells to kill endogenous tumour cells despite the immunosuppressive environment. In this way, we have armed EnAd to
Objective. The objective of this study was to determine the properties of a single-chain bispecific antibody (scBsAb) against human ovarian carcinoma and to develop this agent for potential use in human ovarian cancer.. Methods. ELISA and FACS were performed to determine the antigen-binding properties of the scBsAb. Its abilities to retarget the preactivated human peripheral blood mononuclear cells (PBMCs) to human ovarian carcinoma cell line SKOV3 cells and mediate their lysis in vitro were performed by a colorimetric MTT-based assay. Nude mice bearing human SKOV3 tumor xenografts were used to study the distribution and imaging of the scBsAb. Its pharmacokinetics in vivo was also studied in naive BALB/c mice.. Results. The scBsAb showed nearly identical ligand binding properties at each site relative to the individual monovalent single-chain antibody prototype molecules and could bridge SKOV3 and human T cell line Jurkat, which expresses CD3 antigens on the surface of cells together. It can ...
Outcomes of acute lymphoblastic leukemia (ALL) in older adults treated with chemotherapy are poor. The CD19/CD3 bispecific T-cell engager (BiTE) antibody blinatumomab is approved for refractory, relapsed or minimal/measurable residual disease (MRD)-positive B-cell ALL, but there is little experience in the upfront setting, including in older patients. We retrospectively analyzed outcomes of blinatumomab monotherapy in five newly diagnosed Philadelphia chromosome-negative B-cell ALL patients over 70 years. Three had cytokine release syndrome, treated with dexamethasone and/or tocilizumab, and four patients had neurotoxicity, treated with dexamethasone, without blinatumomab interruption. All five achieved complete remission (CR) after cycle one, three with undetectable MRD. All five were alive at 8 to 15 months. Three remained in MRD-negative CR. Two relapsed after cycle 3, one with extramedullary disease. In our small cohort of patients over 70 years, blinatumomab was safe initial therapy and ...
Therapeutic monoclonal antibodies [mAbs] have become molecules of choice to treat autoimmune disorders, inflammatory diseases and cancer. Moreover, bispecific/multispecific antibodies that target more than one antigen or epitope on a target cell or recruit effector cells [T cell, natural killer (NK) cell or Macrophage cell] towards target cells have shown great potential to maximize the benefits of antibody therapy. In the past decade, many novel concepts to generate bispecific and multispecific antibodies have evolved successfully into a range of formats from full bispecific immunoglobulin gammas [IgGs] to antibody fragments. Impressively, antibody fragments such as bispecific T-cell engager [BiTE], bispecific killer cell engager [BiKE], trispecific killer cell engager [TriKE], tandem diabody [Tandab] and dual-affinity-retargeting [DART] are showing exciting results in terms of recruiting and activating self-immune effector cells to target and lyse tumor cells. Promisingly, Fc antigen binding fragment
Schematic computer artwork of the monoclonal antibody Blinatumomab, a bi-specific T-cell engager (BiTE). Blinatumomab (trade name) specifically targets the CD19 antigen present on B cells. Blinatumomab enables a patients T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites: a CD3 site for T cells and a CD19 site for the target B cells. CD3 is part of the T cell receptor. The drug works by linking these two cell types and activating the T cell to exert cytotoxic activity on the target cell.Blinatumomab is used as a second-line treatment against acute lymphoblastic leukemia. The background is depicting a cancer cell. - Stock Image C029/1340
Schematic computer artwork of the monoclonal antibody Blinatumomab, a bi-specific T-cell engager (BiTE). Blinatumomab (trade name) specifically targets the CD19 antigen present on B cells. Blinatumomab enables a patients T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites: a CD3 site for T cells and a CD19 site for the target B cells. CD3 is part of the T cell receptor. The drug works by linking these two cell types and activating the T cell to exert cytotoxic activity on the target cell.Blinatumomab is used as a second-line treatment against acute lymphoblastic leukemia. - Stock Image C029/1339
1. Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L. et al. T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer. N Engl J Med. 2016;375:2255-62 2. Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today. 2015;20:838-47 3. Topp MS, Gökbuget N, Stein AS, Zugmaier G, OBrien S, Bargou RC. et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. The Lancet Oncology. 2015;16:57-66 4. Goebeler ME, Bargou R. Blinatumomab: a CD19/CD3 bispecific T cell engager (BiTE) with unique anti-tumor efficacy. Leuk Lymphoma. 2016;57:1021-32 5. Klinger M, Benjamin J, Kischel R, Stienen S, Zugmaier G. Harnessing T cells to fight cancer with BiTE® antibody constructs-past developments and future directions. Immunological reviews. 2016;270:193-208 6. Stieglmaier J, Benjamin J, Nagorsen D. Utilizing the BiTE (bispecific T-cell engager) platform for immunotherapy of cancer. ...
New York, USA - August 26, 2019 - As a professional provider occupied in the antibody field for over 10 years, Creative Biolabs is committed to offering highly efficient bispecific antibodies (BsAbs) for industrial and scientific clients all round the world for the BsAbs applications in Oncology, Immunology, Diagnostics, Gene Therapy, Hematology, Ophthalmology, and Osteology.. As engineered macromolecules with two or more distinct binding specificities within one molecule, bispecific antibodies are mostly known for its application in cancer treatment by interfering with signaling pathways, redirecting cytotoxic immune cells, or delivering radioactive therapeutics, most of which act through T cell recruitment and NK cell recruitment, designed to bind tumor-associated antigens and CD3 or CD16/CD56. As an experienced antibody expert, Creative Biolabs is capable of offering BiTE, Triomab, DART, TandAb, and Tandem scFv-Fc BsAb in oncology to block a signaling pathway and its backup pathway, or one ...
Bispecific antibodies, which simultaneously recognize two different antigens, hold great therapeutic potential, but their broad application has been hindered by difficulties in developing stable antibody platforms, favorable pharmacokinetic properties and feasible large-scale manufacturing protocols. In this study, researchers from Genentech Inc. have taken a step in overcoming these problems, improving upon a previously used small-scale strategy, known as knobs-into-holes, that employed sterically complementary mutations in the antibody heavy chain CH3 domain to promote heavy chain heterodimerization with a single common light chain to prevent heavy chain/light chain mispairing. The researchers adapted this technology into a two-part strategy that consists first of small-scale generation of bispecific antibodies lacking a common light chain and hinge disulfides to facilitate proof-of-concept studies, followed by the identification of a common light chain-bispecific antibody for large-scale ...
Get access to 25 years of experience in bispecific antibody development. 3 therapeutic antibodies on the market, 30+ in preclinical and clinical phases including bispecific antibodies.
[127 Pages Report] Check for Discount on Global Bispecific Antibody Sales Market Report 2016 report by QYResearch Group. Notes: Sales, means the sales volume of Bispecific Antibody Revenue,...
Global Bispecific Antibody Market To Surpass USD 10 Billion By 2026 Global Bispecific Antibody Market Opportunity, Drug Sales &
Kinase inhibitors such as ibrutinib have advanced treatment of chronic lymphocytic leukemia (CLL). However, there remains a need for adjunct treatments capable of deepening response or overcoming resistance to kinase inhibitors. CD19/CD3 bispecific antibodies (bsAbs) recruit endogenous T cells to form cytolytic synapses with CD19+ tumor cells. Blinatumomab, a CD19/CD3 bsAb designed in the 54 kDa BiTE format, is FDA approved for the treatment of some forms of acute lymphoblastic leukemia, and has potential for use in other B-cell malignancies. However, due to its short half-life of 2.1 hours, blinatumomab requires continuous intravenous dosing for efficacy. We have developed a novel CD19/CD3 bsAb in the 100 kDa single chain-Fv Fc format (19/3-scFv-Fc). With a half-life of approximately 7 days, 19/3-scFv-Fc may be suitable for weekly dosing, providing a significant logistical advantage. Here we investigated the potential use of 19/3-scFv-Fc for treatment of CLL. We first cultured peripheral blood ...
Tumor vaccines have to provide several signals for T cell activation. Among them, signal 1 (through TCR/CD3) and signal 2 (through CD28) are the most important. We herein describe a procedure to introduce anti-CD3 and anti-CD28 signals into any tumor cell which is susceptible to infection by Newcastle disease virus (NDV). We developed the ATV-NDV tumor vaccine which consists of patient-derived tumor cells (ATV) modified through infection by NDV. We tested for further improvement of vaccine efficiency the addition of two bispecific single-chain antibodies. They bind with one arm to the viral hemagglutinin-neuraminidase (HN) or fusion (F) protein of NDV expressed at the surface of the vaccine cells while the second arm is directed either against CD3 or CD28 of T cells. The aim of this study was to optimize the coupling of these new reagents to the tumor vaccine. When anti-CD3 and anti-CD28 molecules bind to the same anchoring viral molecule (e.g. HN), competition for binding could occur under ...
Manufacturer: Amgen. The antibody is a bispecific T-cell engager that binds to CD19 on the surface of cells in B-lineage origin and CD3 expressed on the surface of T-cells. Blinatumomab activates endogenous T-cells by connecting to CD3 in the T-cell receptor complex with CD19 on benign and malignant B-cells. The formation of a cytolytic synapse between the T-cell and the tumour cell causes the release of proteolytic enzymes, which kills both proliferating and resting target cells.. Patients may receive 2 cycles of treatment. A single cycle of treatment is 4 weeks of continuous infusion. followed by a 2-week treatment-free interval. Patients who have achieved complete remission after 2 treatment cycles may receive up to 3 additional cycles of blinatumomab treatment, based on an individual risk-benefit assessment.. ...
This is a randomised, open-label, multicenter, phase III study for adult de novo Ph+ ALL patients (≥18 years, no upper age-limit) based on the combination of the pan-TKI Ponatinib, with the bispecific monoclonal antibody Blinatumomab. The control arm will be represented by a chemotherapeutic scheme combined with Imatinib for patients aged 18-65 and by Imatinib plus age-adjusted chemotherapy for elderly patients (,65 years old).. Patients (≥18 years, no upper age limit) will be randomized 2:1 to receive the experimental or control arm. If patients in the control arm do not achieve a CHR and/or MRD negativity, after the sixth consolidation cycle (week 20), a crossover to receive Blinatumomab is planned. Likewise, if patients in the control arm develop an ABL1 mutation at any time of treatment, they will switch to experimental arm. HLA typing will be performed immediately after diagnosis in both arms for patients aged up to 65 years.. After the 2 cycles of Blinatumomab in the experimental arm ...
Persistence or recurrence of minimal residual disease (MRD) after chemotherapy results in clinical relapse in patients with acute lymphoblastic leukemia (ALL). In a phase 2 trial of B-lineage ALL patients with persistent or relapsed MRD, a T cell-engaging bispecific Ab construct induced an 80% MRD response rate. In the present study, we show that after a median follow-up of 33 months, the hematologic relapse-free survival of the entire evaluable study cohort of 20 patients was 61% (Kaplan-Meier estimate). The hema-tologic relapse-free survival rate of a subgroup of 9 patients who received allogeneic hematopoietic stem cell transplantation after blinatumomab treatment was 65% (Kaplan-Meier estimate). Of the subgroup of 6 Philadelphia chromosome-negative MRD responders with no further therapy after blinatumomab, 4 are in ongoing hematologic and molecular remission. We conclude that blinatumomab can induce long-lasting complete remission in B-lineage ALL patients with persistent or recurrent MRD. The
Zymeworks Doses First Patient in Phase 1 Trial of ZW25, a Novel Bi-Specific Antibody. Vancouver, BC, September 26, 2016--Zymeworks Inc., a biopharmaceutical company discovering and developing innovative multi-functional protein-based therapeutics, including bi-specific antibodies and drug conjugates for the treatment of cancer, announced today that the first patient was dosed in a Phase 1 clinical trial of ZW25 for treatment of HER2-expressing tumors.
The HER2 protooncogene encodes a 185-kD transmembrane phosphoglycoproteins, human epidermal growth factor receptor 2 (p185HER2), whose amplified expression on the cell surface can lead to malignant transformation. Overexpression of HER2/p185HER2 is strongly correlated with progression of human ovarian and breast carcinomas. Recent studies have shown that human T cells can be targeted with bispecific antibody to react against human tumor cells in vitro. We have developed a bispecific F(ab)2 antibody molecule consisting of a humanized arm with a specificity to p185HER2 linked to another arm derived from a murine anti-CD3 monoclonal antibody that we have cloned from UCHT1 hybridoma. The antigen-binding loops for the anti-CD3 were installed in the context of human variable region framework residues, thus forming a fully humanized BsF(ab)2 fragment. Additional variants were produced by replacement of amino acid residues located in light chain complementarity determining region 2 and heavy chain ...
polyneuropathy (1 grade 3), edema (1 grade 3), and pyrexia (1 grade 1). No anti-AMG 420 antibodies were detected at doses up to 800 μg/d. Six patients had a complete response, 1 each at 6.5, 100, and 200 µg/d, and 3 at 400 µg/d; responses were ongoing for the past 3 months. There also were 2 partial remissions, a partial response at 50 µg/d, and a very good partial response at 800 µg/d. All 3 patients treated at 400 µg/d had an MRD-negative complete response.. Clinical Implications: AMG 420 showed evidence of clinical activity in patients with relapsed or refractory multiple myeloma. No major toxicities were observed up to 400 µg/d, and that is the recommended dose for further investigation; dose-limiting toxicities at 800 µg/d were cytokine-release syndrome and peripheral polyneuropathy. (Also, refer to Abstract 592, which highlights the activity of AMG 701, another anti-BCMA bispecific T-cell engager.4) The bispecific T-cell engager technology has already shown efficacy in leukemia and ...
Clinical trial for childhood ALL , Efficacy and Safety of the BiTE Antibody Blinatumomab in Chinese Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)
This application note describes how HTRF® and High throughput LabChip® ProteinEXact ensure a rapid and accurate characterization of bispecific antibodies (bsAbs).
Bispecific antibodies are a versatile class of targeted therapeutics designed to bind two different sites, which can be located on a single antigen or on two antigens. Although bispecific antibodies were conceptualized ~60 years ago, various challenges associated with protein engineering, stability and manufacturing delayed their wide-spread development. However, as of 2020, numerous validated platforms, i.e., those that have produced bispecific clinical candidates, are readily available (1). Using these platforms, the commercial clinical pipeline has grown to over 100 bispecific antibodies, ranging from tandem single-chain variable fragments (scFv) to full-length immunoglobulins with dual variable domains. Substantial growth in the pipeline has occurred only relatively recently, though. During the early 2010s, bispecific antibodies comprised less than 10% of the total number of antibody therapeutics entering clinical study per year, but this number rose to 25% by 2018. Reflecting the general ...
Hofmann M, Große-Hovest L, Bässler T, Pyz E, Bamberg ML, Aulwurm S, Bühring H-J, Schwartz K, Haen S, Schilbach K, Rammensee H-G, Salih HR and Jung G. Generation, selection and preclinical characterization of an Fc-optimized FLT3-antibody for the treatment of myeloid leukemia. Leukemia 26:1228-1237 (2012) Große-Hovest L, Müller S, Minoia R, Wolf E, Zakhartchenko V, Wenigerkind H, Lassnig C, Besenfelder U, Müller M, Lytton SD, Jung G, Brem G. Cloned transgenic farm animals produce a bispecific antibody for T cell mediated tumor cell killing. Proc Natl Acad Sci USA 101,6858-6863 (2004) Große-Hovest L, Hartlapp I, Marwan W, Brem G, Rammensee HG, Jung G. A recombinant bispecific single chain antibody induces targeted, supra-agonistic CD28 stimulation and tumor cell killing. Eur J Immunol 33, 1334-1340 (2003) Jung G, Große-Hovest L, Krammer PH, Rammensee HG. Target cell restricted triggering of the CD95 (APO-1/Fas) death receptor with bispecific antibody fragments. Cancer Res 61,1846-1848 ...
This phase III trial studies how well blinatumomab works in combination with chemotherapy in treating patients with or without Down syndrome and newly diagnosed, standard risk B-lymphoblastic leukemia or B-lymphoblastic lymphoma. Monoclonal antibodies, such as blinatumomab, may induce changes in bodys immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as vincristine, dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine, mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin decreases the toxic effects of methotrexate. Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving blinatumomab and combination chemotherapy may work better then combination chemotherapy alone in treating patients with B-ALL. This
Blinatumomab is a cancer medicine that interferes with the growth and spread of cancer cells in the body. Blinatumomab is used to treat a certain type of acute lymphoblastic leukemia. This medicine is given after other cancer treatments have been tried without success. Blinatumomab was approved by the US Food and Drug...
After adoptive transfer of pre-activated lymphocytes into the operation cavity of glioma patients, tumor regression and improved survival have been reported in some patients. Results were most impressive when bispecific antibodies with tumor x CD3 specificity were also applied. In this study, we att …
Therapeutic antibodies have improved treatments of complex diseases such as cancer, viral infections and inflammatory diseases over the past three decades, due to their unique ability to specifically home in on surface proteins. A new generation of biologically engineered antibody drugs - bispecifics - combine the binding specificity of two antibodies in only one molecule. Roche has invented the CrossMAb technology to produce bispecific antibodies. Theres one cell line, and one production process; its just one molecule from the start.
Merus is using its Biclonics technology platform to generate differentiated therapeutics in the form of full length human IgG bispecific antibodies designed to recruit the immune system to eliminate cancer cells. 0 0 Academic Web Pages Academic Web Pages2016-05-01 00:00:002016-05-01 00:00:00Distinct HIV-1 Neutralization Potency Profiles of Ibalizumab-Based Bispecific Antibodies. ...
Bispecific antibodies are an alternative option for the treatment of certain types of cancer. They may also be used for more effective medical imaging.
A homogenous sample of identical bispecific antibody determinants, each determinant being composed of two L-H half-molecules linked by disulfide bonds, each L-H half-molecule being specific for a diff
The aim of the present study was to assess the feasibility of a 3D tumor cell culture model, that is, multicellular tumor spheroids (MCTSs) as an adequate model for micrometastases and therefore as a pharmacological model for efficacy testing of trifunctional therapeutic antibodies. Unlike conventio …
Summary of Facts and Submissions. I. Appeal lies from the decision of the examining division to refuse the European patent application No. 04739378.0, entitled Pharmaceutical compositions comprising bispecific anti-CD3, anti-CD19 antibody constructs for the treatment of B-cell related disorders.. II. The examining division considered a main request and an auxiliary request and held that the subject-matter of claim 1 of both lacked inventive step.. III. With the statement of grounds of appeal the appellant submitted a main and two auxiliary requests.. IV. The board issued a communication pursuant to Article 15(1) RPBA, in which objections inter alia under Articles 56 and 84 EPC were raised by the board (Article 111(1) EPC).. V. In reply, the appellant submitted a letter dated 30 August 2016, accompanied by a new main request, and renumbered the previous main request as auxiliary request 3. The appellant later informed the board that he would not be represented at the oral proceedings.. VI. Oral ...
Bispecific T cell engager (BiTE®) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the bodys immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE® antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE® antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit About ...
Monoclonal antibodies (mAbs) are currently among the best remedies in the treatment of cancer disorders. Almost 12 anti-cancer therapeutic mAbs have been approved for clinical applications. Although mAbs have been found to target specific antigens, numerous impediments are emerged in cancer therapy by mAbs because of expression of a low level of the same antigens on the surface of normal cells. To exterminate tumor cells specifically, the current paper puts forward a novel strategy to target cancer cells more selectively by bispecific monoclonal antibody (bsmAb), which has an affinity against the tumor-specific antigens. Translocations in genes and chromosomes are known triggers for the development of human cancers. The mutations in gene profile could create novel tumor-specific proteins and receptors which could be detected using bsmAbs.
Next generation antibodies such as bispecific antibodies (bsAbs) and antibody-drug conjugates (ADC) have reached market maturity demonstrating strong therapeutic benefit for patients. (Diamantis & Banerji, 2016; Garber, 2014) However, targeting broadly expressed, tumor-associated rather than tumor-specific antigens by highly potent ADCs warrants early safety assessment due to the risk of severe on-target side effects in normal tissues. (Diamantis & Banerji, 2016) Recently, it was elegantly shown that tumor selectivity can be increased by bispecific engagement of two antigens and the application of affinity attenuated binding moieties within a bispecific format. (Mazor et al., 2015a; Mazor et al., 2015b; Robinson et al., 2008) In the presented study, simultaneous targeting of two clinically validated cancer antigens, c-MET and EGFR, was evaluated, as receptor cross-talk and signaling redundancies give rise to c-MET mediated resistance mechanism during anti-EGFR monotherapy. (Engelman et al., ...
Immatics is a clinical-stage biopharmaceutical company spearheading the development of advanced immunotherapies that are active against multiple cancer indications. Based in Tuebingen, Germany and Houston, Texas, the company has recognized that novel, better and safer targets are the key to developing future cancer immunotherapies. Immatics has revolutionized the identification and qualification of novel, proprietary and tumor-specific peptide antigens (TUMAPs) through its world-leading target and TCR discovery platform XPRESIDENT®. TUMAPs significantly expand the target space for immuno-oncology as they are not limited to surface proteins, which are the targets of classical antibodies or CAR-T therapies. Immatics believes that by using its TUMAP expertise it can unlock the significant potential of immuno-oncology drugs, such as adoptive cellular therapies, biologicals and vaccines to improve the treatment of a wide range of cancers.. Immatics pipeline includes several TCR-bispecifics and ...
IMCgp100, an anti-CD3 antibody fragment fused to a gp100-specific T cell receptor, yielded long-lasting responses in patients with advanced melanoma.
... Interim Phase 1 Data Presented at International Conference on Malign... Lymphomas Shows Dose Dependent Single Agent Activity ...BETHESDA Md. June 5 /- Micromet Inc. (Nasdaq...In the study relapsed incurable non-Hodgkins lymphoma (NHL) patient...,Micromets,BiTE,Antibody,Blinatumomab,(MT103/MEDI-538),Demonstrates,Durable,Responses,in,Patients,with,Relapsed,Non-Hodgkins,Lymphoma,medicine,advanced medical technology,medical laboratory technology,medical device technology,latest medical technology,Health
Adults with relapsed/refractory B-cell precursor ALL were randomized in a 2:1 ratio to receive blinatumomab or 1 of 4 pre-specified, investigator-chosen, SOC chemotherapy regimens. Randomization was stratified by age (, 35 years vs ≥ 35 years of age), prior salvage therapy (yes vs no), and prior allogeneic HSCT (yes vs no) as assessed at the time of consent.. The study consisted of up to a 3-week screening and pre-phase period, a treatment period consisting of induction with 2 cycles of either blinatumomab or SOC chemotherapy, a consolidation phase of up to 3 additional cycles of protocol-specified therapy, and a maintenance phase for up to an additional 12 months with protocol-specified therapy. A safety follow-up visit 30 days after the last dose of protocol-specified therapy and a long-term follow-up period were included. The long-term follow-up part of the study was discontinued prematurely based on a recommendation from the data monitoring committee (DMC) that the study be stopped for ...
2.1.2 If superiority of blinatumomab in the MRD positive group is shown, to compare the OS of blinatumomab in conjunction with chemotherapy to chemotherapy alone in patients with BCR-ABL-negative B cell precursor ALL who are MRD negative after induction and intensification chemotherapy, based on MFC assessment of residual blasts ...
Starting with a hybridoma cell line or antibody sequence, we can deliver from milligrams to grams of your custom bispecific antibodies. 100% royalty-free.
On December 3, 2014, blinatumomab (Blincyto) was granted accelerated approval for use in treating Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).1,2. Supporting Trial. Approval was based on results of a single-arm trial in 185 patients showing achievement of durable complete remission/complete remission with partial hematologic recovery. Blinatumomab was administered by continuous infusion for 4 weeks of a 6-week cycle. In the first cycle, the initial dose was 9 µg/d for week 1, then 28 µg/d for the remaining 3 weeks. The target dose of 28 µg/d was administered in cycle 2 and subsequent cycles starting on day 1 of each cycle.. Among treated patients, the median age was 39 years (range, 18-79 years), 34% had undergone hematopoietic stem cell transplantation prior to receiving blinatumomab, and 17% had received more than two prior salvage therapies.. Complete remission/complete remission with partial hematologic recovery within two ...
TY - JOUR. T1 - Enhanced ADCC and NK cell activation of an anticarcinoma bispecific antibody by genetic insertion of a modified IL-15 cross-linker. AU - Schmohl, Joerg U.. AU - Felices, Martin. AU - Taras, Elizabeth. AU - Miller, Jeff S.. AU - Vallera, Daniel A.. N1 - Funding Information: We acknowledge the excellent technical assistance of Deborah Todhunter, Andy Sicheneder, Sami Chu, and Seunguk Oh. This work was supported in part by the US Public Health Service Grants R01-CA36725, R01-CA72669, P01-CA65493, P01-CA111412 and R35 CA197292 awarded by the NCI and the NIAID, DHHS. It was also supported by an NIH Research Evaluation and Commercialization Hub (REACH) Award (U01), the Mayo Partnership Award, the Lion Fund, William Lawrence and Blanche Hughes Fund, the Randy Shaver Foundation, the Atwater Cancer Drug Development Award, a CETI translational award from the University of Minnesota Masonic Cancer Center (D.A.V.) and the Deutsche Krebshilfe (111548) (J.U.S.). D.A.V. and J.S.M. are members ...
Global Bispecific Antibody Sales Market Report 2016 is a market research report available at US $4000 for a Single User PDF License from RnR Market Research Reports Library.
Micromets BiTE antibody blinatumomab (MT-103) elicits a high response rate in acute lymphoblastic leukemia patients with minimal residual disease, according to the Berlin-based company. The German Multicenter Acute Lymphoblastic Leukemia Study Group (GMALL) presented phase II clinical data involving the drug at the 2009 Congress of the European Hematology Association in Berlin. 1
This single-centre trial evaluated the efficacy of intraperitoneal catumaxomab in outpatients with malignant ascites related to epithelial tumours.
Clinical trial for Lymphoma , A Phase 1b Open-Label Study Investigating the Safety and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Relapsed/Refractory Indolent Non-Hodgkins Lymphoma
In this study, we show that bispecific tandem ScFv against human CTLA-4 can have an unexpected biological effect by revealing the plasticity for signaling through the cytoplasmic domain of this surface receptor. On one hand, when CTLA-4 binds B7.1 or B7.2 in the context of coligation with the TCR, it transduces a signal that inhibits T cell activation (reviewed in Refs. 1 , 2 , and 4, 5, 6). On the other hand, we show in this study that binding of a bispecific tandem ScFv ligand of CTLA-4 causes the same cytoplasmic domain to transduce a signal that, by itself, activates the T cell without the need for coligation of the TCR. Although triggered by different ligands that bind to different sites on CTLA-4, both responses involve PP2A. The inhibitory function of CTLA-4 correlates with a decrease in its association with PP2A (19), while the activating function of CTLA-4 correlates with an increase in its association with PP2A.. Activation of T cells by 24:26 is not the result of functional blockade ...
Key clinical point: A bispecific anti-CD19, anti-CD20 chimeric antigen receptor (CAR) T cell approach is safe and produced complete responses in the majority of patients with relapsed or refractory non-Hodgkin lymphoma.Major finding: Eleven of 17 assessable patients had a response to treatment, and of those 11 patients, 9 had complete responses, all of which are ongoing.Study details: A phase 1 study of 17 patients with relapsed or refractory B-cell non-Hodgkin lymphomas.
The characterization of novel therapeutic antibodies with multivalent or multispecific binding sites requires new measurement modalities for biosensors, to discriminate the engagement of antigens via one, two, or even more binding moieties. The presentation of antigens on a sensor surface in a well-controlled spatial arrangement is a prerequisite for the successful interpretation of binding kinetics measurements of multivalent analytes, but the adjustment of defined distances between immobilized ligands is difficult to achieve in state-of-the-art biosensor systems. Here, we introduce a simple DNA nanostructure resembling a slingshot, which can be configured with two identical or two different antigens (bivalent or bispecific), which are spaced at a defined distance. We characterize the slingshot structure with a chip-based biosensor using electrically switchable DNA nanolevers and demonstrate that bivalent and monovalent antibodies selectively interact with slingshots that have been ...
Methods are provided for making bispecific antibodies and antibody conjugates comprising site-specifically cross-linking two or more antibodies, antibody fragments or Fc-fusion proteins. Also provided
Integral Molecular, the industry leader in the discovery of monoclonal antibodies (MAbs) against membrane proteins, and Merus N.V. (Nasdaq:MRUS), a clinical-stage immuno-oncology company developing innovative bispecific antibody therapeutics, announced that they have entered into a collaboration on multiple undisclosed targets.
Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal ...
A recent development in immunomanipulation involves the targeting of cytotoxic T lymphocytes (CTL) to cell-bound antigens using bispecific antibodies. These antibodies have been engineered such that specificity is directed against the T cell receptor (TCR) or TCR-associated T3 molecules, as well as against the chosen antigen. The present study was aimed to force interactions between T and B cells by bridging their receptors. F23.1 antibodies, which are specific for gene products of the TCR V beta 8 gene family, were conjugated with TNP (2,4,6-trinitrophenyl) and this construct was used to bridge the receptors of V beta 8+ T cells with the receptors of TNP-specific B cells. The bridging was demonstrated by direct killing of both a TNP-specific B hybridoma and of blast cells from mice transgenic for mu, kappa of the TNP-specific antibody Sp6. Further, F23.1-TNP constructs in conjunction with V beta 8+ CTL were shown to specifically deplete Ig-secreting B cells from Sp6 transgenic mice. Conjugates ...
Angiopoietin-2 (Ang-2) is released from endothelial cells only in response to stimulus (e.g. wound healing, tumor growth) and facilitates blood vessel sprouting and inhibits pericyte-endothelial cell interaction via Tie2 signaling. In tumors, Ang-2 is up-regulated and acts together with the VEGF/VEGFR2 pathway to stimulate tumor angiogenesis and metastasis. While therapeutic intervention using antagonists to the VEGF/VEGFR2 pathway has proven to be successful in limiting disease progression in a number of different clinical settings, there is an obvious need for an improved response. In various preclinical mouse angiogenesis or xenograft models, the combination treatment with anti-Ang2 antibody and the VEGF/VEGFR blocker provided additional benefit over inhibiting the individual pathway. Here as an alternative to combo therapy, we have engineered a tetravalent IgG-scFv bispecific antibody, LY3207447. LY3207447 is an immunoglobulin G4 (IgG4) antibody, comprising of VEGFR2 antibody derived from ...
Influenced by rising strategic alliances, collaborations, advancements in the field of ADCs and bispecific antibodies, the market for cancer mAbs will grow...
advanced flow cytometry, cytokine release, T cell activation, bispecific antibodies, Incucyte® Live-Cell Analysis, iQue® advanced flow cytometry, Immunotherapy, immune systems, cancerous cells, T cell biology, Clare Szybut
I am currently working with Dr Vijay Chudasama on the discovery and application of novel chemistry for protein manipulation and bioconjugation, with a particular focus on exploring highly controlled methods for incorporating antibody targeting ligands onto nanoparticle surfaces. My primary research (EPSRC i-sense Exploratory Project), in close collaboration with Professor Molly Stevens and Professor Rachel McKendry, is focused on the development of highly sensitive nanoparticle-based diagnostic devices for the early detection of viral diseases. In addition to this I am actively involved in several secondary projects, including; developing therapeutic nanoparticles, decorating microparticles, generating bispecific antibody therapeutics, exploring new antibody modification strategies, peptide modification, and developing novel synthetic organic pathways.. ...
Purpose: PI3K/AKT/mTOR network adaptation through the upregulation of receptor tyrosine kinases signaling and subsequent re-activation of AKT is a common resistance mechanism to chemotherapies and small molecule inhibitors of mammalian target of rapamycin (mTOR). In order to block this feedback loop, MM-141, a tetravalent bispecific antibody directed at IGF-1R and ErbB3, was co-administered in combination with everolimus in various preclinical models of cancer. As everolimus is an approved therapy for women with advanced hormone receptor-positive breast cancer after failure of treatment with aromatase inhibitor, we have specifically focused on the analysis of a MM-141/everolimus combination in a hormone refractory breast cancer mouse model.. Experimental Procedures: Estrogen-supplemented mice bearing BT-474-M3 ER+/PR+ breast cancer xenografts were implanted with tamoxifen-releasing pellets. Following the development of resistance to tamoxifen, these mice were randomized into pharmacodynamics and ...
SAN DIEGO--(BUSINESS WIRE)-- Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announces it has entered into an agreement with venBio Partners, a venture capital group focused on building and funding portfolio companies with potential first- and best-in-class therapeutic product applications, which permits venBios portfolio companies to enter into a pre-agreed worldwide OmniAb platform license agreement. Under any platform license agreement, venBios portfolio companies will be able to use the full OmniAb platform including OmniRat®, OmniMouse®, OmniFlic® and OmniChicken™ to discover fully human mono- and bispecific antibodies. Ligand is eligible to receive access payments, development and regulatory milestone payments, and tiered royalties for each product incorporating an OmniAb antibody. venBios future portfolio companies will be responsible for all costs related to the programs. This deal represents an OmniAb first in terms of enabling a venture investor to incubate a series of ...
Research Interests: Developing targeted imaging and therapeutic agents designed to improve the detection and treatment of cancer. Specific research interests include (i) developing new nanoformulations that are capable of carrying extremely high payloads of drugs, radiosensitizing agents, and/or contrast agents; (ii) investigating new targeting strategies that maximize specificity and sensitivity; and (iii) developing new bioconjugation techniques that enable the highly efficient, site-specific labeling of antibodies and other targeting ligands and that allow for the rapid production of bispecific antibodies ...
Native mass spectrometry preserves the structural integrity of a biomolecule, and can provide valuable information associated with a proteins multi-meric state, stoichiometry of complexes, and non-covalent interactions with other proteins or small molecules. The less complex spectra typically generated with native MS, such as narrow charge distributions and relatively few charge states, permit a convenient visualization of the various species that are present in the sample mixture. We utilize the excellent resolving power of an orbital ion trap mass spectrometer to interrogate biomolecular complexes and other pharmacological moieties through traditional intact molecular mass determinations under partially denaturing conditions paired with native mass spectrometry. This combination of analyses has facilitated process improvements for a plethora of antibody engineering exercises including single cell co-expression of bispecific antibody products by the low level detection of mispaired species. ...
UTRECHT, The Netherlands, July 28, 2017 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq:MRUS), a clinical-stage immuno-oncology company developing innovative bispecific antibody therapeutics (Biclonics®), today announced that the U.S. Court of Appeals for the Federal Circuit affirmed the trial courts conclusion that Regeneron Pharmaceuticals, Inc. engaged in inequitable conduct before the United States Patent and Trademark Office while prosecuting U.S. Patent No. 8,502,018 (018 patent), entitled Methods of Modifying Eukaryotic Cells. In todays decision, the Federal Circuit ruled fully in favor of Merus, affirming that Regenerons 018 patent is unenforceable, having been obtained by inequitable conduct. The Federal Circuit noted Regeneron made false assertions, relied on a misleading presentation, and withheld material information from the United States Patent Office, and further, that Regenerons litigation misconduct obfuscated its prosecution misconduct. We are pleased by today
unique single-chain, tri-specific NK cell engager (TriKE) and tetra-specific NK cell engager (TetraKE) platforms targeting hematologic malignancies, sarcomas and carcinomas (solid tumors). The presentation will address both the TriKE and TetraKE constructs, as well as our second-generation anti-CD16-IL-15-anti-CD33 TriKE (OXS-C3550); another first-of-its-kind, single-chain, tri-specific NK cell engager (TriKE).. NK cell cancer-killing activity is expected to be increased by bringing the NK cells in close proximity to the cancer cells. This may be achieved by engagers that bind to CD16 on the surface of NK cells and bind specific proteins (such as CD33) on the surface of cancer cells, thus forming an immune synapse between the NK cell and the cancer cell. Our lead TriKE, anti-CD16-IL-15-anti-CD33 (OXS-3550) is expected to be in the clinic in the second half of 2018. The TriKE constructs utilize the inclusion of interleukin-15 (IL-15), a peptide that leads to proliferation and activation of the ...
These are modest amounts for a biotech, where it can take millions of dollars and several years of plugging away to sniff success. And Avitide has some hurdles ahead: Its trying to build a business through partnerships, and convince a variety of pharma and biotech companies to use its technology to help make various biologics, from vaccines and bi-specific antibodies to the viral vectors, or delivery vehicles, used in gene therapy. But Isett says that the uptake so far has Avitide believing itll be profitable in the next one to two years. He wont identify Avitides partners, only saying they are large biotech and pharmaceutical companies, and that the projects Avitide is working on are varied. Some companies want help with preclinical drug candidates, while others are prepping to launch a drug and need help making more of it.. The demand for the technology has increased significantly, and quite frankly were scaling to actually meet that challenge, he says. The company currently has 17 ...
Treatment of prostate cancer cells with anti-PSCA antibody 1G8 results in cell death and in vivo growth suppression by a Fc-independent mechanism of action. These results are similar to those reported for the anti-epidermal growth factor receptor (EGFR) antibody 225, the murine parental antibody of the chimeric clinical antibody Erbitux ( 12). Fan et al. showed that both native 225 and its F(ab′)2 fragment could inhibit in vivo growth of EGFR-positive tumors, although the activity was less sustained and less complete (∼50%) than native antibody. The partial loss of 225s activity was attributed to the more rapid pharmacodynamic turnover of F(ab′)2. In contrast, 1G8s F(ab′)2 was equal to or even superior to native 1G8 both in vitro and in vivo. The reasons for this phenomenon are not known, as we too predicted that F(ab′)2 should be less active because of its higher rate of turnover. One possible explanation that we have noted is that F(ab′)2 of 1G8 is internalized more rapidly into ...
SUMOylation of VEGFR2 Regulates Its Intracellular Trafficking and Pathological Angiogenesis Researchers showed that endothelial-specific deletion of the SUMO endopeptidase SENP1 reduced pathological angiogenesis and tissue repair during hindlimb ischemia, and VEGF-induced angiogenesis in the cornea, retina, and ear. SENP1-deficient endothelial cells showed increased SUMOylation of VEGFR2 and impaired VEGFR2 signaling. [Nat Commun] Full Article Targeting the Tie2-αvβ3 Integrin Axis with Bi-Specific Reagents for the Inhibition of Angiogenesis The bi-specific antagonists targeting both Tie2 and αvβ3 integrin inhibited adhesion and proliferation of endothelial cells cultured together with the αvβ3 integrin ligand vitronectin, as well as endothelial cell invasion and tube formation. [BMC Biol] Full Article Phenotypic miRNA Screen Identifies miRNA-26b to Promote the Growth and Survival of Endothelial Cells Scientists revealed that miR-26b enhanced endothelial cell growth and survival through ...
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
Late-onset Alzheimers disease (AD) accounts for the majority of AD cases. A characteristic feature of AD is the accumulation of β-amyloid (Aβ) plaques in the brain. Several mutations are associated with risk for late-onset AD, particularly mutations in the genes encoding apolipoproteins APOE4 and clusterin (also known as APOJ), which alter the metabolism and impair the clearance of Aβ. Mutations in the gene encoding TREM2 (triggering receptor expressed on myeloid cells 2), a protein with a single transmembrane domain that is present in microglia in the brain, are also associated with increased risk of AD. Yeh et al. found that the three risk factors are mechanistically linked. A protein microarray screen using a library of secreted ligands immobilized on glass slides and a fusion antibody construct containing the extracellular domain of TREM2 or TREM1 identified various lipoproteins as potential selective ligands of TREM2. These included low-density lipoprotein, lipidated APOE and lapidated ...
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I really cant catch a break, can I?. My latest BCR-ABL blood test that detects my cancers genetic mutation came back ever so slightly positive (like 0.01%). This isnt a relapse but rather just some pesky cancer cells that refuse to take a hint.. To treat this, I will be taking a very specialized drug called Blinatumomab. Its administered as a continuous 28 day drip which means Ill have to carry around a portable IV pump. Ill then get a 2 week break before a second 28 day infusion. If Im disconnected from the pump for more than 4 hours, I may have to start the whole 28 day cycle over again. What a pain.. This Sunday Ill be admitted to the hospital for 3 or 4 days of monitoring to make sure that I dont have any negative reactions to the medication.. As for my vision issues, depressingly there hasnt really been any improvement. If anything Ive gotten more blind spots that make it hard to see things that Im directly looking at.. Ive been unable to work or drive, both of which I ...
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Special Report on behavioral search retargeting, along with research on current topics, trends and surveys relating to Behavioral Search Retargeting
In this white paper Chango shares insights on how search retargeting (the fastest growing form of retargeting) is used for acquisitions, prospecting, and competitor conquests.
2016 - 2019. [37] Byeongjun Yu, Dobeen Hwang, Hyungsu Jeon, Hyungjun Kim, Yonghyun Lee, Hyeongseop Keum, Jinjoo Kim, Dong Yun Lee, Yujin Kim, Junho Chung, Sangyong Jon. A hybrid platform based on a bispecific peptide-antibody complex for targeted cancer therapy Angewantde chemie. 2019 Feb 11:58(7):2005-2019 (IF 12.257). [36] Hyungjun Kim, Dobeen Hwang, Minsuk Choi, Soyoung Lee, Sukmo Kang, Yonghyun Lee, Sunghyun Kim, Junho Chung, and Sangyong Jon. Antibody-assisted delivery of a peptide-drug conjugate for targeted cancer therapy Molecular Pharmaceutics. 2018 Dec 6:16(1):165-172 (IF 4.396). [35] Joon Nam*, Yonghyun Lee*, Yejin Yang, Seongkeun Jung, Wooseong Kim, Jin-Wook Yoo, Jeon-Ok Moon, Changyong Lee, Hae Young Chung, Minsoo Kim, Sangyong Jon, and Yunjin Jung. Is it worth expending energy to convert biliverdin into bilirubin? Free Radical Biology and Medicine. 2018 Aug 20;124:232-240. (IF 5.657). *These authors contributed equally to this work.. [34] Soyoung Lee, Yonghyun Lee, Hyungjun ...
Multiple Myeloma data from EHA. Oncologists provide insights on data for carfilzomib, daratumumab, isatuximab, melflufen‎, selinexor, venetoclax, and a BCMA-CD38 bispecific CAR-T.
BEVERLY HILLS, Calif.--(BUSINESS WIRE)-- GT Biopharma, Inc. (OTCQB: GTBP) (GTBP.PA) an immuno-oncology company focused on innovative therapies based on the Companys proprietary NK cell engager (TriKE™) technology platform today announced the pricing of an underwritten public offering of 4,300,000 Units, consisting of one share of its common stock and one warrant to purchase one share of its common stock, at a public offering price of $5.50 per Unit or Pre-Funded Unit, as applicable. In addition, the Company has granted the underwriters a 45-day over-allotment option to purchase up to an additional 645,000 Units, less underwriting discounts and commissions. At the option of the purchasers in the offering in certain circumstances, in lieu of issuing a Unit, the Company may issue a Pre-Funded Unit, consisting of one pre-funded warrant to acquire one share of its common stock and one warrant to purchase one share of its common stock. The offering is expected to close on February 16, 2021, subject ...
Quality assessment of image retargeting results is useful when comparing different methods. However, performing the necessary user studies is a long, cumbe
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Bionic asked for help extending their presence in the UK market, learn how Bant implemented a successful messaging & retargeting campaign.
"Zymeworks Announces Updated Single Agent Data for HER2-Targeted Bispecific Antibody ZW25 at European Society for Medical ... Holmes, David (2011). "Buy Buy Bispecific Antibodies". Nature Reviews Drug Discovery. 10: 798. doi:10.1038/nrd3581. PMID ... development and commercialization of bispecific antibodies across multiple disease areas.The extended agreement has meant that ... "Improving biophysical properties of a bispecific antibody scaffold to aid developability". mAbs. 5 (5): 646-654. doi:10.4161/ ...
The furthest developed of these are bispecific tandem di-scFvs, known as bi-specific T-cell engagers (BiTE antibody constructs ... "Expression and purification of monospecific and bispecific recombinant antibody fragments derived from antibodies that block ... Kufer, Peter; Lutterbüse, Ralf; Baeuerle, Patrick A. (2004). "A revival of bispecific antibodies" (PDF). Trends in ... Hollinger, Philipp; Prospero, T; Winter, G (July 1993). ""Diabodies": small bivalent and bispecific antibody fragments". ...
Baeuerle, Patrick A.; Reinhardt, Carsten (2009-06-15). "Bispecific T-Cell Engaging Antibodies for Cancer Therapy". Cancer ... "Bispecific T-cell engaging antibodies for cancer therapy". Cancer Research. 69 (12): 4941-4944. doi:10.1158/0008-5472.CAN-09- ... and the development of bispecific T-cell engaging antibodies for therapy of cancer. Baeuerle earned his diploma in biology from ... "Reinventing the Antibody". The Scientist. Retrieved 2017-10-04. Perkel, Jeffrey (2008-08-14). "New Lymphoma Drug Shows Promise ...
31 (4). Guy DG, Uy GL (October 2018). "Bispecific Antibodies for the Treatment of Acute Myeloid Leukemia". Curr Hematol Malig ... Flotetuzumab (INN; development code MGD006) is a bispecific antibody designed for the treatment of acute myeloid leukemia. This ... a focus on monoclonal antibodies and immune checkpoint inhibitors". Curr. Opin. Hematol. 25 (2): 136-145. doi:10.1097/MOH. ... "Integrated Pharmacokinetic/Pharmacodynamic Model of a Bispecific CD3xCD123 DART Molecule in Nonhuman Primates: Evaluation of ...
These bispecific monoclonal antibodies are sometimes referred to as mAb2. Antibody Fab region Protein tag Janeway, CA, Jr.; et ... Fcab fragments can be inserted into a full immunoglobulin by swapping the Fc region, thus obtaining a bispecific antibody (with ... This property allows antibodies to activate the immune system. In IgG, IgA and IgD antibody isotypes, the Fc region is composed ... By contrast, the Fc region of all antibodies in a class are the same for each species; they are constant rather than variable. ...
... (MM-141) is an experimental monoclonal antibody for the treatment of cancer. It is a bispecific antibody targeting ...
The beginning of the pretargeting concept was based on bispecific antibodies which were able to bind a specific target antigen ... Owing to the high molecular weight of antibodies and the Fc domain of the antibody, a slow clearance from the blood and non- ... However, these types of antibodies turned out to be quite troublesome, due to the triggering of the human anti-murine antibody ... "Recombinant Bispecific Monoclonal Antibodies Prepared by the Dock-and-Lock Strategy for Pretargeted Radioimmunotherapy". ...
Another technology recently developed is the OkapY bispecific antibody technology. MorphoSys' OkapY technology is a new ... bispecific antibody format with the hysicochemical properties to simplify the development and large-scale production of such ... Two antibodies developed by MorphoSys are already approved and marketed. Tafasitamab (MOR208) is a humanized monoclonal ... The company has various antibody, protein and peptide technologies that it uses to discover and develop both proprietary and ...
One of them is development of bispecific antibodies such as CD3/CLL-1 antibody. It can recruit unstimulated primary T cells in ... February 2017). "An anti-CD3/anti-CLL-1 bispecific antibody for the treatment of acute myeloid leukemia". Blood. 129 (5): 609- ...
2014). "Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface". Nature Biotechnology ... designed fusions for bispecific antibodies, and progress toward vaccines. DeLano Award for Computational Biosciences Feynman ...
This approach is similar to the one taken in the development of bispecific monoclonal antibodies. In a study, the plasma half- ... Since they are not structurally related to antibodies, they are classified as a type of antibody mimetic. Avimers have been ... Half-life can be increased by binding them to antibodies. A library theoretically containing up to 1023 different A domains ... They have improved heat stability compared with antibodies, but limited plasma half-life because of their smaller size. ...
... (INN) is a bispecific monoclonal antibody that is being investigated for diabetic macular edema. This drug is being ...
Morecki S, Lindhofer H, Yacovlev E, Gelfand Y, Slavin S (Feb 2006). "Use of trifunctional bispecific antibodies to prevent ... Krolick KA, Uhr JW, Slavin S, Vitetta ES (Jun 1982). "In vivo therapy of a murine B cell tumor (BCL1) using antibody-ricin A ... Herman Waldmann, Slavin was the first to introduce the use of an anti-CD52 monoclonal antibody (CAMPATH-1; Alemtuzumab and ... focusing on the use of activated donor lymphocytes targeted against cancer with monoclonal and bispecific antibodies for ...
Genentech was able to demonstrate in mouse models that the new bispecific antibody was able to reach therapeutic levels in the ... They utilized a mouse bispecific antibody with two active sites performing different functions. One arm had a low-affinity anti ... Researchers at Genentech proposed the creation of a bispecific antibody that could bind the BBB membrane, induce receptor- ... This way, the amount of transported antibody is based on the concentration of antibody on either side of the barrier. The other ...
2017-08-24). "Bispecific T cell engager (BiTE®) antibody constructs can mediate bystander tumor cell killing". PLOS ONE. 12 (8 ... similar to additional in vitro work using bispecific antibodies performed at Amgen. Some reports have suggested that the ... Fas was first identified using a monoclonal antibody generated by immunizing mice with the FS-7 cell line. Thus, the name Fas ... This event is also mimicked by binding of an agonistic Fas antibody, though some evidence suggests that the apoptotic signal ...
Bispecific antibody fragments, such as anti-CD19/CD16, allow the targeting of immunotherapeutic drugs to the cancer cell. Anti- ... These receptors bind to the Fc portion of IgG antibodies, which then activates antibody-dependent cell-mediated cytotoxicity ( ... In addition, CD16 could play a role in antibody-targeting cancer therapies. FcγRIV, a murine homologue of CD16A has been shown ... After binding to ligands such as the conserved section of IgG antibodies, CD16 on human NK cells induce gene transcription of ...
NI-1701, an anti-CD47, anti-CD19 bispecific antibody in development for treatment of B-cell hematological cancers. NI-1801, an ... anti-mesothelin bispecific antibody in the preclinical phase of development for treatment of solid tumors. No drugs have been ... NI-0401, an anti-CD3ε antibody being developed in partnership with Tiziana Life Sciences. Phase II trials in patients with ... "First in Human Study of an Anti-Toll-like Receptor 4 (TLR4) Monoclonal Antibody (NI-0101) in Adult Healthy Volunteers - Full ...
Nithiyanandam developed a bispecific antibody composed of two different Fab' fragments: one fragment from an anti-oligomeric ... Nithiyanandam's bispecific antibody is conjugated to a quantum dot with MRI and fNIR detection capabilities. Nithiyanandam's in ... vitro studies suggest that the bispecific antibody quantum dot conjugate has little cross-reactivity and could potentially ...
... is a bi-specific monoclonal antibody composed of two different heavy chains and two different light chains. One arm ... Vanucizumab (INN; development code RG7221) is an experimental humanized monoclonal antibody designed for the treatment of ... The antibody is designed to inhibit both VEGF-A and Ang2 simultaneously to offer superior clinical benefit compared to VEGF-A ... of the antibody binds Angiopoietin-2 (Ang2) and the other is based on bevacizumab (Avastin), binding Vascular Endothelial ...
... the antibody-drug conjugates based on hYP7 and the T-cell engaging bispecific antibodies derived from YP7 and GC33, have been ... October 2017). "An anti-glypican 3/CD3 bispecific T cell-redirecting antibody for treatment of solid tumors". Science ... These antibodies have been humanized (e.g. hYP7) using antibody engineering for clinical applications. The Ho lab has also ... The YP7 murine antibody has been humanized and named as 'hYP7'. GPC3 is also expressed to a lesser degree in melanoma, ovarian ...
In-vitro and in-vivo activity of CIK cells in conjunction with bispecific antibodies, cross-linking cytotoxic effector cells ... "Cytokine-induced killer cells targeted by the novel bispecific antibody CD19xCD5 (HD37xT5.16) efficiently lyse B-lymphoma cells ... "Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: ... Indeed, the engagement of CD16a on CD3+CD56+ cells led to a potent antibody-dependent cell-mediated cytotoxicity (ADCC) both in ...
Blinatumomab, a CD19-CD3 bi-specific monoclonal murine antibody, currently shows promise as a novel pharmacotherapy. By ... The cDNA is sequenced and the sequence encoding the variable heavy and variable light chains of these antibodies are cloned ... In this therapy, mice are immunized with the CD19 antigen and produce anti-CD19 antibodies. Hybridomas developed from mouse ... An extensive panel of monoclonal antibodies to cell surface markers, particularly CD or cluster of differentiation markers, are ...
"Anti-CD3-based bispecific antibody designed for therapy of human B-cell malignancy can induce T-cell activation by antigen- ... making it a type of bispecific antibody. They are fragments antigen-binding (Fab or Fab') of two different monoclonal ... Development and characterisation of bispecific antibody derivatives for the immunotherapy of CD19-positive leukaemia and ... Bi-specific T-cell engagers employ a similar mechanism of action while being cheaper. Karpovsky, B.; Titus, J. A.; Stephany, D ...
... a bispecific antibody, inhibits tumor progression and angiogenesis". mAbs. 8 (5): 892-904. doi:10.1080/19420862.2016.1171432. ... "Anti-Nogo-A antibodies prevent vascular leakage and act as pro-angiogenic factors following stroke". Scientific Reports. 9 (1 ...
... (trade name Hemlibra) is a humanized bispecific antibody for the treatment of haemophilia A, developed by Chugai (a ... May 2016). "Factor VIII-Mimetic Function of Humanized Bispecific Antibody in Hemophilia A". The New England Journal of Medicine ... a novel factor VIII-mimetic bispecific antibody, in healthy subjects". Blood. 127 (13): 1633-41. doi:10.1182/blood-2015-06- ...
TaiMed inked licensing agreement with the ADARC for bispecific monoclonal antibody technology. Park, Alice (25 January 2010). " ...
Like other bispecific antibodies, and unlike ordinary monoclonal antibodies, solitumab forms a link between T cells and its ... June 2009). "Antitumor activity of an EpCAM/CD3-bispecific BiTE antibody during long-term treatment of mice in the absence of T ... Solitomab (INN; development code MT110) is an artificial bispecific monoclonal antibody that is being investigated as an anti- ... It is a fusion protein consisting of two single-chain variable fragments (scFvs) of different antibodies on a single peptide ...
"Targeting of indium 111-labeled bivalent hapten to human melanoma mediated by bispecific monoclonal antibody conjugates: ...
March 2007). "CD19-/CD3-bispecific antibody of the BiTE class is far superior to tandem diabody with respect to redirected ... It belongs to a class of constructed monoclonal antibodies, bi-specific T-cell engagers (BiTEs), that exert action selectively ... Blinatumomab is a bispecific T-cell engager (BiTE). It enables a patient's T cells to recognize malignant B cells. A molecule ... "Amgen Receives FDA Breakthrough Therapy Designation For Investigational BiTE Antibody Blinatumomab In Acute Lymphoblastic ...
Sun LL (2015). "Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies". Sci Transl Med. 7 ... Kim CH (2013). "Bispecific small molecule-antibody conjugate targeting prostate cancer". PNAS. 110 (44): 17796-17801. Bibcode: ... Frankel SR (2013). "Targeting T cells to tumor cells using bispecific antibodies". Curr Opin Chem Biol. 17 (3): 385-392. doi: ... In addition to antibody fragments, non‐antibody‐based approaches have also been used to direct CAR specificity, usually taking ...
Blinatumomab, a CD19-CD3 bi-specific monoclonal murine antibody, currently shows promise as a novel pharmacotherapy. By ... In this therapy, mice are immunized with the CD19 antigen and produce anti-CD19 antibodies. Hybridomas developed from mouse ... An extensive panel of monoclonal antibodies to cell surface markers, particularly CD or cluster of differentiation markers, are ... The cDNA is sequenced and the sequence encoding the variable heavy and variable light chains of these antibodies are cloned ...
An antibody can be called monospecific if it has specificity for the same antigen or epitope,[48] or bispecific if they have ... Antibody mimetic[edit]. Antibody mimetics are organic compounds that, like antibodies, can specifically bind antigens. They are ... Asymmetrical antibodies[edit]. Heterodimeric antibodies, which are also asymmetrical and antibodies, allow for greater ... How Lymphocytes Produce Antibody from Cells Alive!. *Antibody applications Fluorescent antibody image library, University of ...
Whole antibody. *bispecific: Trifunctional antibody. Fab fragment. *F(ab')2 fragment / Fab' fragment ... Fab antibodies also have diagnostic use. Arcitumomab is a mouse antibody that recognizes Carcinoembryonic antigen, an antigen ... The antigen-binding fragment (Fab) is a region on an antibody that binds to antigens. It is composed of one constant and one ... An antibody digested by pepsin yields two fragments: a F(ab')2 fragment and a pFc' fragment ...
Muller K.M (1998). "The first constant domain (CH1 and CL) of an antibody used as heterodimerization domain for bispecific ... Antibody mimeticEdit. Antibody mimetics are organic compounds that, like antibodies, can specifically bind antigens. They are ... How Lymphocytes Produce Antibody from Cells Alive!. *Antibody applications Fluorescent antibody image library, University of ... Asymmetrical antibodiesEdit. Heterodimeric antibodies, which are also asymmetrical and antibodies, allow for greater ...
Bi-specific T-cell engager source is the species on which the protein sequence of the antibody is based: source. output ... Monoclonal antibody drugs[మార్చు]. Set the parameter type=mab. This form of the box uses a different subset of parameters, mab_ ... Shortened Monoclonal antibody form: {{Infobox drug , type = mab , image = , alt = , mab_type = ,!-- mab, Fab, F(ab')2, Fab', ... Full Monoclonal antibody template with extended fields: {{Infobox drug , type = mab , image = , width = , alt = , image2 = , ...
The most promising neutralizing agent is a bispecific monoclonal antibody that entered a first-in-human clinical trial in 2019 ... The Ho Lab is funded by two NIH grants to pursue the use of engineered antibodies to purge the viral latent reservoir as a part ... Ho's group has also engineered exquisitely potent antibodies that neutralize divergent strains of HIV. ...
... bispecific antibodies technologies, single B cell screening technology), antibody engineering (antibody humanization, affinity ... GenScript ProBio provides solutions for antibody drug development including antibody drug discovery (hybridoma, antibody ... "Duke-NUS, GenScript and A*STAR launch first-in-the-world SARS-CoV-2 serology test to detect neutralising antibodies without ... "GenScript Announces Publication of Clinical Data On New Method for Detecting COVID-19 Neutralizing Antibodies In Nature ...
... and bispecific antibodies primarily directed at clinically-validated targets for which the current standard of care is ... antibodies, and novel antibody-based proteins. The XpressCF+ platform allows for precise incorporation of non-natural amino ... To date, Sutro's drug discovery efforts have focused on antibody-drug conjugates, cytokine-based immuno-oncology therapies, ... internally-developed antibody drug conjugates, or ADCs. STRO-001 is an ADC targeting CD74, a protein highly expressed in ...
... antibodies, bispecific MeSH D12.776.377.715.548.114.143 - antibodies, blocking MeSH D12.776.377.715.548.114.167 - antibodies, ... antibodies MeSH D12.776.377.715.548.114.071 - antibodies, anti-idiotypic MeSH D12.776.377.715.548.114.107 - antibodies, ... antibodies, helminth MeSH D12.776.377.715.548.114.191 - antibodies, heterophile MeSH D12.776.377.715.548.114.224 - antibodies, ... hiv antibodies MeSH D12.776.377.715.548. - htlv-i antibodies MeSH D12.776.377.715.548. - htlv-ii ...
... a monoclonal antibody antagonist of the glucagon receptor for type 2 diabetes (T2DM) REGN4018, a novel MUC16xCD3 bispecific T- ... a monoclonal antibody against PCSK9 designed to reduce LDL cholesterol RN6G, a monoclonal antibody against Beta amyloid for the ... a monoclonal antibody against nerve growth factor for the treatment of pain Ponezumab (codenamed RN1219), a monoclonal antibody ... "REGN4018, a novel MUC16xCD3 bispecific T-cell engager for the treatment of ovarian cancer". "FIH study of an OX40 agonist mAb ...
He received his doctorate in 1992 with a thesis on immunotherapy for tumor cells (bispecific monoclonal antibodies for the ... This company developed the monoclonal antibody Zolbetuximab, which is to be used against esophageal and gastrointestinal cancer ... 1487-1495, doi:10.1093/annonc/mdz199, ISSN 1569-8041, PMC 6771222, PMID 31240302 Antibody Shines in Advanced Gastric Cancer, ...
... antibodies, bispecific MeSH D12.776.124.486.485.114.143 - antibodies, blocking MeSH D12.776.124.486.485.114.167 - antibodies, ... antibodies, bispecific MeSH D12.776.124.790.651.114.143 - antibodies, blocking MeSH D12.776.124.790.651.114.167 - antibodies, ... antibodies MeSH D12.776.124.486.485.114.071 - antibodies, anti-idiotypic MeSH D12.776.124.486.485.114.089 - antibodies, ... antibodies, helminth MeSH D12.776.124.486.485.114.191 - antibodies, heterophile MeSH D12.776.124.486.485.114.224 - antibodies, ...
... an acronym for bi-specific T-cell engagers, a class of specific modified antibodies BITE Model (Behavior, Information, Thought ...
Antitumor Activity of a Novel Bispecific Antibody That Targets the ErbB2/ErbB3 Oncogenic Unit and Inhibits Heregulin-Induced ...
... hence the name of bispecific antibodies. This antibody fragment is part of the modular antibody technology of F-star ... Fcabs are antibodies fragments engineered from the constant region of an antibody (Fc). In naturally occurring antibodies (such ... This type of antibodies are therefore able to recognise two different antigens, one at their Fab region and a second one at the ... Fc fragments with engineered HER2/neu-binding sites and antibody properties". Protein Eng Des. 23 (4): 289-297. doi:10.1093/ ...
Bispecific Antibodies. Bispecific Antibodies combine two or more antigen-recognizing elements into a single construct, able to ... The DutaMab™ technology platform further enables the development of bi-specific antibodies on a single arm of the antibody that ... Monoclonal Antibodies. Monoclonal Antibodies (MAbs) are antibodies that are made by identical immune cells, cloned from a ... we also have designed a new format for bispecific antibodies, called CrossMAbs (where MAb stands for Monoclonal Antibody). In ...
Bispecific antibodies capable of simultaneously binding two targets have been studied for many years with a view to their ... Camel single-domain antibodies as modular building units in bispecific and bivalent antibody constructs. J. Biol. Chem. 276 (10 ... Trifunctional Triomab ® antibodies for cancer therapy. In: Bispecific Antibodies. Ed. Kontermann R.E. Berlin: Springer-Verlag, ... Development of tetravalent, bispecific CCR5 antibodies with antiviral activity against CCR5 monoclonal antibody-resistant HIV-1 ...
Platforms for creating higher-order antibodies are streamlining development, reducing risks for patients, and optimizing tumor ... Here, newly engineered bispecific and multispecific antibodies will be put to the test. Such antibodies may engage two or more ... Bispecific, Multispecific Antibodies Grapple with Cancer. Platforms for novel antibody constructs take hold in cancer ... Moving from mono- to bispecific antibodies. One company that is leveraging its success in developing monospecific antibodies ...
Roche has invented the CrossMAb technology to produce bispecific antibodies. Theres one cell line, and one production process ... A new generation of biologically engineered antibody drugs - bispecifics - combine the binding specificity of two antibodies in ... Therapeutic antibodies have improved treatments of complex diseases such as cancer, viral infections and inflammatory diseases ... Bispecific antibodies currently are in clinical trials. 60%. of bispecific antibodies in clinical trials are bringing immune ...
The bispecific antibody 9202.1/5411 lowers histamine release from RBL cells transfected with human FcεRI and human FcγRIIb and ... Bispecific antibodies, which simultaneously recognize two different antigens, hold great therapeutic potential, but their broad ... They used their strategy to successfully generate a bispecific antibody that inhibits the activation of the high affinity IgE ... Development of a Two-part Strategy to Identify a Therapeutic Human Bispecific Antibody That Inhibits IgE Receptor Signaling ...
Bispecific antibody targeting prostate cancer. Chan Hyuk Kim, Jun Y. Axup, Brian R. Lawson, Hwayoung Yun, Virginie Tardif, Sei ... Bispecific antibody targeting prostate cancer. Chan Hyuk Kim, Jun Y. Axup, Brian R. Lawson, Hwayoung Yun, Virginie Tardif, Sei ... Bispecific small molecule-antibody conjugate targeting prostate cancer. Chan Hyuk Kim, Jun Y. Axup, Brian R. Lawson, Hwayoung ... Bispecific small molecule-antibody conjugate targeting prostate cancer Message Subject (Your Name) has sent you a message from ...
Antibody drug conjugates and bispecific antibodies allow the selective targeting of potent small molecule toxins or cytotoxic T ... Bispecific antibody targeting prostate cancer. Chan Hyuk Kim, Jun Y. Axup, Brian R. Lawson, Hwayoung Yun, Virginie Tardif, Sei ... Bispecific antibody targeting prostate cancer. Chan Hyuk Kim, Jun Y. Axup, Brian R. Lawson, Hwayoung Yun, Virginie Tardif, Sei ... chemically defined bispecific antibodies (17). In an effort to explore further semisynthetic approaches to generate bispecific ...
Bispecific Antibodies - Antibodies developed in the laboratory to recognize more than one protein on the surface of different ... Examples include bispecific antibodies 2B1, 520C9xH22, mDX-H210, and MDX447, is clearly explained in Medindia s glossary of ... Medical Word - Bispecific Antibodies. Ans : Antibodies developed in the laboratory to recognize more than one protein on the ... Bispecific Antibodies - Glossary. Written & Compiled by Medindia Content Team. Medically Reviewed by The Medindia Medical ...
Research will focus on applying the bispecific platform to target immuno-oncology checkpoints, with pre-clinical data set to be ... Home Drug Discovery Antibodies Immune Pharma Licenses Bispecific Antibody Technology from Atlante Biotech ... The bispecific antibody demonstrated direct anticancer effects in vitro, as well as in vivo antitumor activity and improved ... Immune Pharma Licenses Bispecific Antibody Technology from Atlante Biotech. December 28, 2015. 0 ...
Bispecific monoclonal antibody entry in the public domain NCI Dictionary of Cancer Terms Bispecific+antibodies at the US ... "A review of bispecific antibodies and antibody constructs in oncology and clinical challenges". Pharmacology & Therapeutics. ... Two bispecific antibodies are presently in clinical use. Blinatumomab, which targets CD19 and CD3, is used in the treatment of ... A bispecific monoclonal antibody (BsMAb, BsAb) is an artificial protein that can simultaneously bind to two different types of ...
1. A pharmaceutical composition comprising a bispecific single chain antibody construct, said bispecific single chain antibody ... said bispecific single chain antibody construct in said CHO cell and recovering the produced bispecific single chain antibody ... the antibody construct as claimed was a monomeric bispecific single-chain antibody molecule, as also reflected by the molecular ... This is the same arrangement as the claimed antibody constructs. The antibody disclosed in document D3 is not bispecific, ...
... by Lisa M. Jarvis November 30, 2019 , APPEARED IN VOLUME 97, ISSUE 47 ... a bispecific antibody that targets B-cell maturation antigen, and to add six targets to the firms existing discovery deal. ...
The clinical application of such a combined therapy with ATV-NDV vaccine cells and bi-specific antibodies allows to modify the ... We tested for further improvement of vaccine efficiency the addition of two bispecific single-chain antibodies. They bind with ... Optimization studies for the coupling of bispecific antibodies to viral anchor molecules of a tumor vaccine ... This was not the case when the bispecific reagents bound to separate viral molecules (HN or F, respectively). When using ...
A bispecific antibody containing a 4G7 hybridoma secreting IgG1 antibody specific for B-lymphocytes and a monoclonal antibody ... bispecific antibody 4G7xH22 A bispecific antibody containing a 4G7 hybridoma secreting IgG1 antibody specific for B-lymphocytes ... and a monoclonal antibody targeting Fc gamma RI-expressing cells. Check for active clinical trials using this agent. (NCI ...
Bispecific antibodies are being studied in the imaging and treatment of cancer. ... A type of antibody that can bind to two different antigens at the same time. ... bispecific antibody listen (BY-speh-SIH-fik AN-tee-BAH-dee) A type of antibody that can bind to two different antigens at the ... Bispecific antibodies are being studied in the imaging and treatment of cancer. They are made in the laboratory. ...
... we investigate the potential of an engineered tandem bispecific broadly neutralizing antibody (bs-bnAb) as an innovative ...
Computationally Designed Bispecific Antibodies using Negative State Repertoires. Title: Computationally Designed Bispecific ... Computationally Designed Bispecific Antibodies using Negative State Repertoires Journal Article - in collection Leaver ... Computationally Designed Bispecific Antibodies using Negative State Repertoires. United Kingdom: N. p., Web. doi:10.1016/j.str. ... Computationally Designed Bispecific Antibodies using Negative State Repertoires. United Kingdom. doi:10.1016/j.str.2016.02.013 ...
How bispecific antibodies work. Bispecific monoclonal antibodies harness the activity of the patients own T cells in the bone ... Several bispecific antibodies to treat myeloma are currently under evaluation. But teclistamab is the farthest along in the ... Teclistamab is an anti-BCMA and CD3 bispecific antibody. Dr. Saad Usmani from the Levine Cancer Institute in Charlotte, North ... Teclistamab is an important and promising new bispecific antibody therapy. Further data from the phase II trial are needed to ...
At ASCO, researchers presented preclinical and translational data on GBR 1302 (Glenmark), a HER-2 and CD3 bispecific antibody ... Investigators also presented a trial-in-progress poster about GBR 1342 (Glenmark), a CD38 and CD3 bispecific antibody under ... I think bispecific molecules are showing the promise where you can infiltrate these immune cells into the solid tumors and ... spoke with HemOnc Today at ASCO Annual Meeting about the companys bispecific T-cell engager platform. ...
Novartis has signed a collaboration and licensing deal with California biotech Xencor for access to its bispecific antibody ... Novartis has signed a collaboration and licensing deal with California biotech Xencor for access to its bispecific antibody ... mid single-digit tiered royalties for worldwide sales of the four proprietary Novartis bi-specific molecules, and low single- ... and Novartis also gets global rights to Xencors bispecific technology to develop and commercialise four additional targets, ...
Appointments, Autism, Bi-Specific Antibodies, Bispecific Antibody, Blood Cancers, Genetics, Immunotherapy, Oncology, People on ... Bispecific Antibody, Clinical Trials, Diabetic Macular Edema, Eye Diseases, Monoclonal Antibodies, Ophthalmics, R&D, Retinal ... Bristol Myers Squibb signs antibody pact with Agenus Bispecific Antibody, Bristol Myers Squibb, Business, Clinical Trials, ... proprietary bispecific antibody program, AGEN1777, and a second undisclosed target. AGEN1777 is an Fc-enhancement antibody ...
Increasing numbers of companies are showing curiosity for the development of Bi-Specific Antibodies for the treatment of ... Growing Inclination of Biopharmaceutical Companies towards Bi-Specific Antibodies. ... Bi-specific antibody is one of the most potentially powerful tools which have emerged in the biopharmaceutical industry. The bi ... "Increasing numbers of companies are showing curiosity for the development of Bi-Specific Antibodies for the treatment of ...
Roche group Genentech said its bispecific antibody ACE910 has picked up a breakthrough designation in the US for the ... Roche group Genentech said its bispecific antibody ACE910 has picked up a breakthrough designation in the US for the ... ACE910 is an investigational humanised bispecific monoclonal antibody engineered by Roche group Chugai to mimic the function of ...
has obtained the IND approval from regulators for its HER2 bispecific antibody, KN-026. The phase I trials will commence later ... Home » Alphamabs bispecific antibody gets clinical approval in China. Looking to read the full article? Subscribe to BioWorld. ... has obtained the IND approval from regulators for its HER2 bispecific antibody, KN-026. The phase I trials will commence later ...
... the high potential of bispecific antibodies in the field of immuno-oncology is eliciting a renewed interest from pharmaceutical ... by rapid advances in antibody engineering and the development of several technological platforms such as Triomab or bispecific ... bispecific antibody; cancer immunotherapy; NK cells; T-cells; immune effector cells; immuno-checkpoint bispecific antibody; ... "Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward?" Antibodies 5, no. 1: 1. ...
... Global Bispecific Antibody Market Opportunity, Drug Sales ... 1.2 Overview of Bispecific Monoclonal Antibody. 1.3 Advantage of Bispecific Antibodies upon Monospecific Monoclonal Antibodies ... Global Bispecific Antibody Market Growth: 118% CAGR (2015 -2019). *Global Bispecific Antibody Market Growth In 2019: 280% (, US ... "Global Bispecific Antibody Market Opportunity, Drug Sales & Clinical Trials Insight 2026" Report Highlight:. *Global Bispecific ...
... to antibody fragments. Impressively, antibody fragments such as bispecific T-cell engager [BiTE], bispecific killer cell ... to antibody fragments. Impressively, antibody fragments such as bispecific T-cell engager [BiTE], bispecific killer cell ... Moreover, bispecific/multispecific antibodies that target more than one antigen or epitope on a target cell or recruit effector ... Moreover, bispecific/multispecific antibodies that target more than one antigen or epitope on a target cell or recruit effector ...
... and numerous antibodies have been approved for the treatment of several severe diseases or are currently in clinical... ... Monoclonal antibodies have emerged as an effective therapeutic modality, ... Bispecific antibody Single-chain variable fragment (scFv) Disulfide-stabilized Fv antibody fragment (dsFv) CrossMab Knobs-into- ... Bispecific Antibody Derivatives Based on Full-Length IgG Formats. In: Proetzel G., Ebersbach H. (eds) Antibody Methods and ...
Here, we review the principle of a new class of bispecific antibodies called BiTE (for "bispecific T-cell engager") antibodies ... Evolution of Bispecific Antibodies. More than 25 years ago, monoclonal antibody and recombinant DNA technologies enabled the ... Why Engage T Cells by Bispecific Antibodies?. There is a choice of immunological effector cells for engagement by bispecific ... Why Engage T Cells by Bispecific Antibodies?. *Activity of Antibody-Engaged T Cells against Large Tumors and Disseminated ...
TOKYO:4519) announced results from two global phase lll studies for Chugais bispecific antibody emicizumab (ACE910): ... Chugais Bispecific Antibody Emicizumab to Present Results of Two Pivotal Phase lll Studies at ISTH ... global phase lll studies for Chugais bispecific antibody emicizumab (ACE910): the primary analysis of HAVEN 1 study ( ... Overseas, Chugai Pharmabody Research based in Singapore is engaged in research focusing on the generation of novel antibody ...
  • Monoclonal Antibodies (MAbs) are antibodies that are made by identical immune cells, cloned from a single parent cell. (
  • Cancer immunotherapy with ordinary monoclonal antibodies does not activate T-lymphocytes because the Fab regions are already used for binding the tumour cells, and this type of cell does not have Fc receptors. (
  • Bispecific monoclonal antibodies harness the activity of the patient's own T cells in the bone marrow microenvironment surrounding the myeloma. (
  • Therapeutic monoclonal antibodies have become molecules of choice to treat autoimmune disorders, inflammatory diseases, and cancer. (
  • Monoclonal antibodies have emerged as an effective therapeutic modality, and numerous antibodies have been approved for the treatment of several severe diseases or are currently in clinical development. (
  • To improve their therapeutic potential, monoclonal antibodies are constantly evolved by protein engineering. (
  • Weiner LM, Surana R, Wang S (2010) Monoclonal antibodies: versatile platforms for cancer immunotherapy. (
  • Generation of a BiTE antibody from the variable domains of two distinct monoclonal antibodies is depicted on the left. (
  • MONROVIA, Calif.--( BUSINESS WIRE )-- Xencor Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases, today announced the presentation of new data from multiple preclinical XmAb ® bispecific antibody programs and its preclinical IL-12-Fc cytokine program at the 35th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). (
  • L. G. Lum, R. Rathore, and H. E. Lum, Targeting of Prostate Cancer with T Cells Armed with OKT3 x Anti-HER2/New Bispecific Monoclonal Antibodies(Biabs) , 29 edition, 2001. (
  • As a therapeutic target for HER2-overexpressing cancer ( 4 ), monoclonal antibodies have been developed to target HER2-positive tumors (5-7). (
  • Monoclonal antibodies have emerged as a very successful class of therapeutic agents. (
  • In their native format, monoclonal antibodies are monospecific in that they recognize only one epitope, but their Fc domain also binds to FcfR-expressing cells. (
  • These include three bispecific monoclonal antibodies (bsAbs). (
  • High throughput LabChip ® ProteinEXact ™ to evaluate the fragmentation of monoclonal antibodies after heat stress, and analyze different forms of bsAbs from cell culture supernatants. (
  • First-generation bispecific platforms significantly alter the structure of monoclonal antibodies or rely upon complex and proprietary manufacturing processes. (
  • Azymetric™ bispecifics, in contrast, retain the desirable drug-like qualities of monoclonal antibodies, including long half-life, stability and low immunogenic potential, which increases their probability of success. (
  • 0.01%) and the relatively high nonspecific uptake with the directly labeled monoclonal antibodies (in whole immunoglobulin G or fragment form) used in most studies. (
  • MacroGenics, a Maryland company, is a clinical-stage biopharma that discovers innovative monoclonal antibodies for cancer. (
  • Compared with mAb (monoclonal antibodies), they are proven by many studies to have better potency and improved safety. (
  • It would take only 3-5 months for SMAB screening and evaluation and 14-15 months for preclinical CMC development, which is highly efficient and produces deliverables with equivalent developability as monoclonal antibodies. (
  • Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases, today announced the presentation of new preclinical data from three XmAb ® 2+1 bispecific antibody programs and its IL-12-Fc cytokine program during the second session of the American Association for Cancer Research (AACR) Virtual Annual Meeting. (
  • The third case study examines binary mixtures of monoclonal antibodies with different biophysical properties and how DLS helps investigate whether the antibodies mutually impair their physical stability in solution. (
  • Examine a DLS-based approach to characterizing binary mixtures of monoclonal antibodies. (
  • Otherwise, overt production of inflammatory cytokines and secondary reactions may occur as side effects, as can be observed with constitutively T-cell activating monoclonal antibodies to CD3 or CD28, and with bispecific antibodies bearing Fcγ portions. (
  • scFvs offer several advantages over monoclonal antibodies as carriers of radionuclei and drugs to tumors, including greater tumour penetration due their small size, low kidney uptake, rapid blood clearance and a lower negative response by the human immune system. (
  • Immunotherapies with monoclonal antibodies (mABs) directed against the CD20 antigen have previously been shown to be highly effective. (
  • Fundamentally, their engineered expression platforms focus on streamlining novel antibody development, reducing the risk factors to patients, and optimizing tumor destruction. (
  • Bispecific Antibodies combine two or more antigen-recognizing elements into a single construct, able to bind to two or more targets. (
  • Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. (
  • A bispecific monoclonal antibody (BsMAb, BsAb) is an artificial protein that can simultaneously bind to two different types of antigen. (
  • Naturally occurring antibodies typically only target one antigen. (
  • Expanding on an earlier pact, AbbVie will pay Harpoon Therapeutics $50 million for an option to license HPN217, a bispecific antibody that targets B-cell maturation antigen, and to add six targets to the firms' existing discovery deal. (
  • If you look at solid tumors, where some [chimeric antigen receptor T-cell therapies and checkpoint inhibitors ] have not been effective, I think bispecific molecules are showing the promise where you can infiltrate these immune cells into the solid tumors and actually have an impact," Reddy told HemOnc Today . (
  • Moreover, bispecific/multispecific antibodies that target more than one antigen or epitope on a target cell or recruit effector cells (T cell, natural killer cell, or macrophage cell) toward target cells have shown great potential to maximize the benefits of antibody therapy. (
  • Promisingly, crystallizable fragment (Fc) antigen-binding fragment and monomeric antibody or half antibody may be particularly advantageous to target solid tumors owing to their small size and thus good tissue penetration potential while, on the other hand, keeping Fc-related effector functions such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cell-mediated phagocytosis, and extended serum half-life via interaction with neonatal Fc receptor. (
  • Fab arms are responsible for antigen binding and have been extensively engineered for developing highly specific and synthetic antibodies against numerous targets ( 4 ). (
  • Bostrom J, Yu SF, Kan D et al (2009) Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. (
  • An alternative approach to engage T cells for cancer therapy are antibodies, which are bispecific for a surface target antigen on cancer cells, and for CD3 on T cells. (
  • Pioneering work by Kufer and colleagues ( 6 ) showed that CD3/target antigen-bispecific antibodies of this particular design had an exceptionally high potency, and could likewise engage CD8 + and CD4 + T cells for redirected lysis of cancer cells at very low effector to target (E:T) ratios. (
  • As shown on the right, a BiTE antibody can transiently connect a T cell and a cancer cell by simultaneously binding CD3 and a target antigen. (
  • The end of each arm of the Y-shaped antibody is like a key that binds onto a protein on the surface of the foreign invader called an antigen. (
  • Once an antibody binds to the antigen, it either directly neutralizes the threat itself, or marks the invader so that other cells in the immune system can locate it and remove it from the body. (
  • Instead of binding the same antigen with both arms of the antibody, bispecific antibodies can bind one antigen with one arm and a totally different one with the other arm. (
  • The B7-H3 x CD28 bispecific antibody activated T cells only in the presence of the B7-H3 antigen and did not demonstrate super-agonism, consistent with Xencor's CD28 platform design. (
  • For pretargeting, these peptides were used in combination with a bsMAb composed of the anti-HSG Fab′ that was covalently coupled with the Fab′ of either an anticarcinoembryonic antigen or an anticolon-specific antigen-p antibody to provide tumor targeting capability. (
  • This bispecific antibody format was created by fusing single-domain antibodies directed against the carcinoembryonic antigen and the activating FcγRIIIa receptor to human Cκ and CH1 immunoglobulin G1 domains, acting as a natural dimerization motif. (
  • Studies in nonobese diabetic/severe combined immunodeficient gamma mice xenografted with carcinoembryonic antigen-positive tumor cells showed that Fab-like bispecific molecules in the presence of human peripheral blood mononuclear cells significantly slow down tumor growth. (
  • A monoclonal antibody that binds two different types of antigen. (
  • We constructed a bispecific antibody that is composed of a rapidly internalizing antibody binding to a tumor-associated antigen, ephrin receptor A2 (EphA2), and a noninternalizing antibody binding to a highly expressed tumor-associated antigen, activated leukocyte cell adhesion molecule (ALCAM). (
  • We found that the overall internalization property of the bispecific is profoundly impacted by the relative surface expression level (antigen density ratio) of EphA2 versus ALCAM. (
  • When the EphA2-to-ALCAM ratio is greater than a threshold level (1:5), the amount of the bispecific taken into the tumor cell exceeds what is achieved by either the monoclonal internalizing antibody or a mixture of the two antibodies, showing a bispecific-dependent amplification effect where a small amount of the internalizing antigen EphA2 induces internalization of a larger amount of the noninternalizing antigen ALCAM. (
  • We developed a bispecific antibody targeting ephrin receptor A2 (EphA2), a rapidly internalizing antigen, and activated leukocyte cell adhesion molecule (ALCAM), a non- or slowly internalizing antigen, and found that the bispecific becomes internalized when the ratio of EphA2 to ALCAM is greater than approximately 1:5. (
  • In a study of patients with metastatic colorectal cancer, the novel carcinoembryonic antigen T-cell bispecific (CEA-TCB) antibody was evaluated as a monotherapy and in combination with atezolizumab (Tecentriq). (
  • In the present study, a bispecific antibody was designed that links a conventional antigen‑binding fragment (Fab) against cluster of differentiation 3 antigen (CD3) to a camel single domain antibody (VHH) against human epidermal growth factor receptor 2 (HER2). (
  • Distinct from previous studies (28-30), CD3-S-Fab was designed by linking a camel anti-HER2 single-domain antibody (VHH) to the C-terminal of a conventional anti-CD3 antigen-binding fragment (Fab). (
  • A novel carcinoembryonic antigen T-cell bispecific antibody (CEA TCB) for the treatment of solid tumors. (
  • By simultaneously binding to tumor associated antigens (TAAs) and CD3Ɛ, The scFv antibody can retarget surrounding T cells to antigen-expressing tumor cells. (
  • bsAbs are designed to have two specific antigen-binding sites, unlike conventional antibody formats. (
  • After preliminary injection of a bispecific anticarcinoembryonic antigen (CEA) or antihapten antibody (Bs-mAb F6-679), AG 8.1 or AG 8.0 hapten radiolabeled with 188 Re or 125 I was injected into a nude mouse model grafted subcutaneously with a human colon carcinoma cell line (LS-174-T) expressing CEA. (
  • The purpose of this study was to compare the distribution and dosimetry of a bivalent hapten labeled with 188 Re or 125 I after preliminary injection of a bispecific anticarcinoembryonic antigen (CEA) or antihapten antibody into a nude mouse model grafted subcutaneously with a human colon carcinoma cell line (LS-174-T) expressing CEA. (
  • Bispecific antibodies are artificially engineered antibodies capable of binding with two different epitopes of an antigen. (
  • Mosunetuzumab, an -investigational - bispecific antibody, demonstrated activity in preliminary studies of patients with non-Hodgkin lymphoma (NHL), including those who are refractory to or relapsed after third-line chimeric antigen receptor (CAR) T-cell therapy. (
  • CEA TCB (RG7802, RO6958688) is a novel T-cell bispecific antibody, engaging CD3ε upon binding to carcinoembryonic antigen (CEA) on tumor cells. (
  • T-cell bispecific antibodies (TCB), engaging T cells independent of their antigen specificity, constitute a powerful strategy for cancer immunotherapy. (
  • Able to simultaneously co-engage with different antigen targets, these new antibody formats are currently being broadly adopted by the biopharmaceutical industry, primarily for developing the next-generation of oncology and immune system therapies. (
  • Antibody class switching does not affect antigen specificity, retains antigen affinity and allows interaction with different effector molecules. (
  • Radiocurability by targeting tumor necrosis factor-alpha using a bispecific antibody in carcinoembryonic antigen transgenic mice. (
  • To overcome systemic side effects, we used a bispecific antibody (BsAb) directed against carcinoembryonic antigen (CEA) and TNF-alpha to target this cytokine in a CEA-expressing colon carcinoma. (
  • We have developed a semisynthetic method for the production of bispecific antibody-like therapeutics consisting of a small molecule targeting moiety conjugated to an antibody. (
  • The bispecific antibody demonstrated direct anticancer effects in vitro, as well as in vivo antitumor activity and improved survival in a mouse xenograft model of disseminated leukemia, according to data presented at IBC Life Sciences' Antibody Engineering & Therapeutics Conference, held December 7-10 in San Diego. (
  • Novartis has signed a collaboration and licensing deal with California biotech Xencor for access to its bispecific antibody technology and rights to develop and commercialise two of the latter's flagship experimental therapeutics. (
  • In March 2018, Merus N.V. announced the initiation of development of novel bi-specific antibodies for cancer therapeutics. (
  • KN046, the world's first PD-L1 - CTLA-4 bispecific therapeutics, is positioned as the backbone of the second generation of tumor immunotherapy," said Dr. Ting Xu, Chairman of the Board and CEO of Alphamab Oncology. (
  • SEATTLE, April 16, 2018 (GLOBE NEWSWIRE) -- Aptevo Therapeutics Inc. (Nasdaq:APVO), a biotechnology company focused on developing novel oncology and hematology therapeutics, today announced the presentation of new data for APVO436, a bispecific antibody candidate targeting CD123 and CD3, at the American Association for Cancer Research (AACR) 2018 Annual Meeting. (
  • Because of their ability to bind to harmful pathogens, chemicals, or proteins on a cell's surface, lab-engineered antibodies have become the basis of many therapeutics over the past decade. (
  • For a closer look at the design, development, and success of CAR T-cell therapy and bispecific antibodies, The Scientist is bringing together a panel of experts to discuss their research and share insights into the potential these therapeutics hold in the fight against various tumor types. (
  • The partnership is for up to 8 antibody therapeutics including ABL Bio's biologics pipelines and collaboration programs between ABL Bio and I-Mab Biopharma (I-Mab). (
  • Within the past 3 years alone, the FDA has approved 20 novel antibody therapeutics for oncological treatment, with over 300 therapeutic antibodies currently in oncology based clinical trials. (
  • We believe that the achievement of another successful milestone further validates our Azymetric™ platform as a generator of leading-edge bispecific antibody therapeutics, and we look forward to the continued advancement of other therapeutic programs under our agreements with Lilly. (
  • In May 2019, Zymeworks announced that GSK has expanded its 2016 licensing and collaboration agreement for the research, development and commercialization of bispecific antibodies across multiple disease areas.The extended agreement has meant that GSK can have access to Zymeworks' heavy-light chain pairing technology, which enables the development of bispecific and multifunctional therapeutics. (
  • Regeneron is also advancing a broad and deep bispecific antibody platform - which may offer off-the-shelf alternatives to cell-based therapies for both solid tumors and hematologic malignancies. (
  • Use of anti-CD3 × anti-HER2/neu bispecific antibody for redirecting cytotoxicity of activated T cells toward HER2/neu + tumors," Journal of Hematotherapy & Stem Cell Research , vol. 10, no. 2, pp. 247-260, 2001. (
  • Bacac M, Klein C, Umana P. CEA TCB: a novel head-to-tail 2:1 T cell bispecific antibody for treatment of CEA-positive solid tumors. (
  • In solid tumor indications, three bispecific scFvs have entered phase I clinical trial and at least ten other antibodies are being evaluated in preclinical development against an impressive variety of solid tumors (Table 1 ). (
  • Investigational treatments like bispecific antibodies that target a broad spectrum of HER2 expression levels on a variety of tumor tissues while simultaneously engaging tumor-infiltrating T cells have the potential to advance the treatment of these tumors, and may fulfill a substantial unmet medical need. (
  • We identified unique and tumor-specific tyrosine phosphorylation rewiring in tumors resistant to treatment with the irreversible third-generation EGFR-inhibitor, osimertinib, or the novel dual-targeting EGFR/Met antibody, JNJ-61186372. (
  • CEA TCB is a novel IgG-based T-cell bispecific (TCB) antibody for the treatment of CEA-expressing solid tumors currently in phase I clinical trials ( NCT02324257 ). (
  • Empowered by this one-stop bispecific antibody development platform, REMD is actively engineering antibody drugs against tumors, and exploring and shaping the landscape of the next-generation antibody immunotherapy. (
  • Fluorescence reflectance imaging revealed increased ratios of extravascular to vascular fluorescence signals in tumors after treatment with CEA TCB compared with control antibody, suggesting specific targeting, which was confirmed by intravital microscopy. (
  • This was not the case when the bispecific reagents bound to separate viral molecules (HN or F, respectively). (
  • The parties will work together and share development costs for the these drugs, and Novartis also gets global rights to Xencor's bispecific technology to develop and commercialise four additional targets, and a non-exclusive license to use Xencor's XmAb Fc technologies in up to ten molecules. (
  • Over 30 bispecific molecules are currently in different stages of clinical trials and more than 70 in preclinical phase. (
  • This review, therefore, focuses on the progress of Fc engineering in generating bispecific molecules and on the use of small antibody fragment as scaffolds for therapeutic development. (
  • Clearly, the demand for antibody molecules and global sales have been rising rapidly. (
  • More than 25 years ago, monoclonal antibody and recombinant DNA technologies enabled the construction of antibody-based molecules that normally do not occur in nature. (
  • The first bispecific antibodies looked like normal immunoglobin G (IgG) molecules but had their two binding arms equipped with distinct binding specificities. (
  • The composition comprising a population of polyclonal bispecific binding molecules that can target and eliminate a host cell infected with the pathogen. (
  • A homogenous sample of identical bispecific antibody determinants, each determinant being composed of two L-H half-molecules linked by disulfide bonds, each L-H half-molecule being specific for a different antigenic determinant and including at least the F(ab') portion of a monoclonal IgG antibody. (
  • Because most targeting agents have been antibody proteins, they tend to clear much more slowly from the body (usually days) than the low molecular weight effector molecules (usually in min). (
  • In vitro and in vivo characterization of these Fab-like bispecific molecules revealed favorable features for further development as a therapeutic molecule. (
  • Flow cytometry analysis showed that the bispecific F(ab')2 molecules can bind specifically to cells overexpressing p185HER2 and to normal human peripheral blood mononuclear cells bearing the CD3 surface marker. (
  • These bispecific molecules have a potential use as therapeutic agents for the treatment of cancer. (
  • Over the years, REMD has worked closely with GenScript on innovative drug discovery and development, and produced quite a collection of novel antibody molecules. (
  • In addition to supporting established formats, the system can be configured to work with completely novel multi-specific antibody-like molecules, new scaffolds, and proprietary engineering techniques (e.g. (
  • The next-generation of biotherapeutics are built on bispecifics and other innovative, highly engineered large-molecules such as antibody drug conjugates. (
  • We offer a new and unique service of generating antibodies which are hybrids of two (or more) unique antibody molecules. (
  • Such antibodies may engage two or more antigens at once, serving as force multipliers that can exploit opportunities beyond the reach of monospecific antibodies, whether they are deployed solo or in teams. (
  • Bispecific antibodies, which simultaneously recognize two different antigens, hold great therapeutic potential, but their broad application has been hindered by difficulties in developing stable antibody platforms, favorable pharmacokinetic properties and feasible large-scale manufacturing protocols. (
  • Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. (
  • This format retains the traditional monoclonal antibody (mAb) structure of two Fab arms and one Fc region, except the two Fab sites bind different antigens. (
  • Bispecific antibodies also have a higher cytotoxic potential, and bind to antigens that are expressed relatively weakly. (
  • For non-IgG-like bsMabs, their smaller size allows them to reach antigens usually unavailable to conventional antibodies. (
  • A type of antibody that can bind to two different antigens at the same time. (
  • Particularly, the generation of bispecific antibodies raised special interest because of their ability to bind two different antigens at the same time, and the efficiency of these formats has been demonstrated in several clinical and preclinical studies. (
  • The novel part of these new bispecific antibodies is their ability to identify and bind to cancer cells by targeting mutated antigens that often differ from the normal version by only one amino acid. (
  • The data gathered in the present study suggest that this bispecific format may be applied to other tumor antigens to produce bispecific antibodies more efficiently. (
  • T-cell bispecific antibodies are designed to simultaneously bind to T cells and tumor cell antigens, leading to T-cell activation, proliferation, and tumor cell death. (
  • Through Genentech's patented bispecific antibody design technologies, T cells can be physically recruited and linked to tumor surface antigens to elicit an antitumor immune response in patients with cancer. (
  • Bispecific scFv antibodies represent a successful and promising immunotherapy platform that retargets cytotoxic T cells to tumor cells, with one scFv directed to tumor-associated antigens and the other to T cells. (
  • Three distinct types of tumor antigens are considered to optimize specificity and safety in bispecific scFv based treatment: cancer-testis antigens, neo-antigens and virus-associated antigens. (
  • Recombinant bispecific antibodies have also been intensively studied to retarget T cells against highly expressed tumor-associated antigens. (
  • Diamantis & Banerji, 2016) Recently, it was elegantly shown that tumor selectivity can be increased by bispecific engagement of two antigens and the application of affinity attenuated binding moieties within a bispecific format. (
  • Increased selectivity of c-MET x EGFR bispecific antibodies towards tumor models with high expression in both antigens by avidity over normal tissue models was confirmed by mixed cell flow cytometry. (
  • Balancing selectivity and efficacy in bispecific ADCs by affinity and epitope optimization could be a viable route to expand the target space of ADCs to ubiquitously expressed antigens. (
  • It has been demonstrated to be effective for the treatment of hematologic malignancies using directly radiolabeled antibodies targeting differentiation antigens, particularly in the treatment of malignant B cell lymphomas ( 1 , 2 ). (
  • The Azymetric™ platform consists of a library of proprietary amino acid substitutions that enable the transformation of monospecific antibodies into bispecific antibodies, which gives them the ability to simultaneously bind two non-overlapping epitopes, or antigens. (
  • We constructed chimeric proteins that contain in a single polypeptide chain a portion of human B7-2 (CD86) genetically fused to single-chain (sc) Fv antibody domains specific for the tumor-associated antigens epidermal growth factor receptor and the closely related ErbB2 receptor tyrosine kinase. (
  • This is an IgG1-based heterodimeric antibody scaffold that consists of two different heavy chains engineered to exclusively assemble into a single molecule, allowing bi-specific binding to two different antigens or drug targets. (
  • Although CAR T-cell therapies clearly have fight in them, they may cede some anticancer glory to bispecific antibodies (bsAbs). (
  • Bispecific antibodies (bsAbs) pave the way for novel therapeutic modes of action along with potential benefits in several clinical applications. (
  • CD19/CD3 bispecific antibodies (bsAbs) recruit endogenous T cells to form cytolytic synapses with CD19+ tumor cells. (
  • Next generation antibodies such as bispecific antibodies (bsAbs) and antibody-drug conjugates (ADC) have reached market maturity demonstrating strong therapeutic benefit for patients. (
  • Preclinically, BEAT bsAbs demonstrate the potential for more potent activity compared to existing therapeutic antibodies. (
  • The new bispecific antibody class (bsAbs) has emerged as one of the fastest-growing next-generation antibody therapies, due to its high specificity and low toxicity. (
  • Even while monospecific antibody-based checkpoint inhibition therapies and CAR T-cell therapies continue to be improved, bispecific and multispecific antibodies are shaping up as a cancer immunotherapy options that may provide significant advantages. (
  • At present, companies such as Amunix Operating, Invenra, Glycotope, and Xencor are working independently and in collaboration with larger pharmaceutical companies, such as Novartis, Daiichi Sankyo, and Roche, to bring bispecific and higher-order antibodies into the cancer immunotherapy market. (
  • Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward? (
  • Del Bano J, Chames P, Baty D, Kerfelec B. Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward? (
  • 5 T-cell bispecific antibodies targeting a variety of tumor types have become an important component of Genentech's investigational cancer immunotherapy research. (
  • Recombination of a mixture of univalent antibody fragments of different specificity. (
  • Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. (
  • Tested BiTE antibodies were either human- or murine-specific, or had a dual species specificity, referred to as "hybrid BiTE antibody. (
  • In contrast to early-generation therapeutic antibodies, T-cell bispecific antibodies combine the binding specificity of two antibodies in one molecule. (
  • T-cell bispecific-antibody-mediated tumor-cell killing does not require pre-existing immunity and may occur independently of T-cell specificity, activation, and differentiation status. (
  • We have developed a bispecific F(ab')2 antibody molecule consisting of a humanized arm with a specificity to p185HER2 linked to another arm derived from a murine anti-CD3 monoclonal antibody that we have cloned from UCHT1 hybridoma. (
  • Because these are bipartite with variable fragments (Fv) coming from two different genes, a linker sequence was introduced in order to align the two variable domains on a single polypeptide chain, resulting in a so-called single-chain antibody (scFv) (ref. 5 ). (
  • This bispecific antibody format is engineered by combining scFv domains of two different antibodies on one polypeptide linker chain. (
  • Specifically, bispecific antibodies with a single-chain (scFv) form of the CAP256.VRC26.25 V2-glycan (apex) antibody on one antibody arm and a full V3-glycan Fab on the other arm neutralizes more HIV-1 isolates than the bNAbs from which they were derived. (
  • Recombinant Anti-CD64 x Anti-EGFR Bispecific Antibody (Fab-scFv-Fc) requires expression of three polypeptide chains, encoding two heavy chains (Fc-containing chains) and one light chain, respectively. (
  • The Fab of anti-CD64 antibody variable domain is fused to the Fc-knob domain with a hinge region and the same as the scFv of anti-EGFR to the Fc-hole domain, or vice versa. (
  • We offer a range of Antibody Reformatting services and are experienced in producing antibodies in a wide range of formats including scFv, Fab, bispecific and many more. (
  • Based on the Fab and scFv formats as building blocks, we can engineer any antibody to help fit your target product profile. (
  • Single-domain antibody-based and linker-free bispecific antibodies targeting FcγRIII induce potent antitumor activity without recruiting regulatory. (
  • An in depth , integrated SMAB (single-domain antibody fused to monoclonal antibody) case study from rational design to preclinical development. (
  • According to the Agreement, GenScript will allow REMD to use its SMAB (Single-Domain Antibody fused to Monoclonal Ab) Platform, a bispecific antibody platform, to develop novel tumor immunotherapy drugs. (
  • Among various bispecific antibody platforms, GenScript's SMAB Platform is highly distinctive in that it creates such hybrids by fusing sdAb (single-domain antibody) to mAb, the most natural bispecific antibodies in the world that require no sequence mutation and minimum engineering. (
  • Our plan is to generate additional preclinical data with selected bispecific drug candidates in 2016. (
  • At ASCO, researchers presented preclinical and translational data on GBR 1302 (Glenmark) , a HER-2 and CD3 bispecific antibody under investigation for treatment of a variety of HER-2-positive cancers. (
  • The Company is developing these bi-specific antibodies in association with the Vall d'Hebron Institute of Oncology by combining Merus' proprietary Biclonics technology platform with VHIO's expertise in clinical, translational and preclinical research. (
  • In preclinical studies, KN046 has demonstrated excellent anti-tumor efficacy, and its toxicity is significantly reduced compared with the existing CTLA-4 antibody Yervoy (ipilimumab). (
  • New preclinical data presented at this year's AACR Annual Meeting compare Aptevo's second generation bispecific, APVO436, with an Aptevo-generated version of Macrogenics' CD123 x CD3 dual-affinity re-targeting (DART) molecule, MGD006, evaluating T-cell activation, proliferation, cytotoxicity and cytokine secretion. (
  • 23andMe has out-licensed its bispecific monoclonal antibody to Almirall in order to leverage Almirall's expertise in medical dermatology and accelerate the development of this preclinical program. (
  • At SITC, we are presenting new data from multiple preclinical programs, including CD28 bispecific antibodies, our second class of T cell engagers, that we have designed to conditionally co-stimulate T cells when they are bound to tumor cells. (
  • As demonstrated in preclinical models, upon dispersion of T-cell bispecific antibodies, the cytotoxic T cells (seen in red) immediately recognize and begin to destroy the target cancer cells (seen in blue). (
  • Additionally, the dual-targeting of Azymetric™ antibodies has demonstrated synergistic efficacy in preclinical studies through simultaneous binding relative to the application of an equivalent dose of the corresponding monospecific antibodies. (
  • Several preclinical and clinical studies have shown the benefit of using the affinity enhancement system (AES), which associates a bispecific antibody with a bivalent hapten ( Fig. 1 ). (
  • In preclinical models, XmAb 2+1 bispecific antibodies bound preferentially to tumor cells compared to normal cells and effectively recruited T cells to kill tumor cells selectively. (
  • Further data presented from preclinical studies of XmAb30819 in non-human primates demonstrated it was well-tolerated with expected pharmacodynamics and an antibody-like half-life. (
  • MedImmune, the global biologics research and development arm of AstraZeneca, and Abpro, an integrated life sciences company at the forefront of synthetic biology, today announced they have entered into a collaborative agreement to advance the development of a preclinical, novel bispecific antibody targeting angiopoietin-2 and vascular endothelial growth factor (Ang2-VEGF). (
  • Based on this underlying treatment concept and on promising data taken from preclinical results and a small pilot study, an open-label, non-randomized, uncontrolled, dose-escalating phase I/II-study is conducted to evaluate safety and preliminary efficacy of the investigational antibody FBTA05 in combination with DLI for patients suffering from rituximab- and/or alemtuzumab-refractory, CD20-positive low- or high-grade lymphoma after allogeneic SCT. (
  • Bispecific antibodies provide access to new modes of action that have not been possible with single antibodies," says Stefan Weigand, Roche's Global Head of Large Molecule Research. (
  • The essential problem with engineering bispecific antibodies is how to guarantee correct assembly of the parts to deliver only the desired molecule, while omitting unwanted side products. (
  • Now, Roche has taken bispecific technology a step further and developed the next generation in bispecific antibody engineering: CrossMAb, a technology that produces one bispecific molecule-not ten, not four, but just what the scientists need. (
  • 2. The assembly of claim 1 wherein the other said antigenic determinant for which said second bispecific antibody determinant is specific is an antigenic site on a second protein molecule. (
  • This bispecific molecule not only recruits T cells via its one binding arm, but simultaneously activates FcγR + accessory cells via its Fc region. (
  • As an alternative approach we exploited recombinant antibody fragments to localize a costimulatory B7 molecule to the surface of tumor cells. (
  • Genedata Biologics is meeting the challenges of developing these complex multi-specific antibodies by providing new tools to enable more efficient molecule design, production, and characterization. (
  • Therefore, today's biopharmas are faced with generating and testing vastly increased numbers of diverse alternative antibody molecule formats," said Dr. Othmar Pfannes, CEO of Genedata. (
  • 2004. Retargeting of adenoviral infection to melanoma: Combining genetic ablation of native tropism with a recombinant bispecific single-chain diabody (scDb) adapter that binds to fiber knob and HMWMAA. (
  • Catumaxomab, one of the first trifunctional antibodies approved for therapeutic use, binds both CD3 on cytotoxic T cells and EpCAM on human adenocarcinomas. (
  • Blinatumomab, a first-generation CD3-CD19 bispecific T-cell engager, binds to CD19 on the surface of B cells and CD3 expressed on the surface of T cells. (
  • Several bispecific antibodies have been developed to increase the breadth of these antibodies, but typically only one arm of these bispecific constructs binds the HIV-1 envelope glycoprotein trimer (Env). (
  • RG7716 is the first bispecific, monoclonal antibody specifically designed for the eye that simultaneously binds to and inactivates vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2). (
  • Let's take a look at the Blincyto of Amgen approved by FDA and EMA in December 2014, which is a double-specific antibody to CD3 on one end of CD19 that binds to the surface of white blood cell B cells, and on the other end of the surface of T cells. (
  • XmAb13676 is a humanized bispecific antibody that binds both CD20 and CD3 in order to recruit cytotoxic T cells to kill CD20 expressing malignant cells. (
  • Bispecific Abs (bsAb) are promising immunological tools for the elimination of tumor cells in minimal residual disease situations. (
  • Bispecific Abs (bsAb) 3 are regarded as powerful tools for the immunological treatment of malignant cells in a minimal residual disease situation, because single disseminated tumor cells are especially appropriate targets for an immunological attack. (
  • Bispecific antibody is known as bsAb for short. (
  • ACE910 is an investigational humanised bispecific monoclonal antibody engineered by Roche group Chugai to mimic the function of blood coagulation factor VIII, and thus provide a new approach to treating the condition, regardless of whether patients have developed inhibitors. (
  • REGN1979 is a wholly-owned, investigational, full-length bispecific monoclonal antibody designed to trigger tumor killing by binding CD3 on immune system T-cells and CD20 on B-cell malignancies. (
  • Treatment with CEA-TCB (RO6958688), an investigational CEA/CD3 bispecific antibody, showed a favorable safety profile and promising efficacy in patients with heavily-pretreated microsatellite stable (MSS) metastatic colorectal cancer (mCRC), with enhanced efficacy when combined with the PD-L1 inhibitor atezolizumab (Tecentriq), according to findings presented at the 2017 ESMO World Congress on Gastrointestinal Cancer. (
  • Mosunetuzumab is an investigational, humanized, T cell-dependent bispecific antibody designed to engage T cells and redirect their cytotoxic activity against malignant B cells. (
  • 1 Mosunetuzumab is an investigational, full-length, bispecific antibody designed to simultaneously bind to CD20 on the surface of malignant B cells and to CD3ε on cytotoxic T cells, resulting in crosslinking of the TCR and subsequent formation of an immunologic synapse and T-cell activation. (
  • This review focuses on the clinical potential of bispecific antibodies as immune effector cell engagers in the onco-immunotherapy field. (
  • Such bispecific antibodies have been developped to enhance immunotherapy, by bridging tumor cells and T cells, or radioimmunotherapy by combining bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells. (
  • However, despite this exponential growth, most therapeutic antibodies rely on a monomeric immunotherapy based mechanism. (
  • FDA in December 2014 highlighted bispecific single chain variable fragment antibody as powerful and promising platform for immunotherapy both in hematologic and solid tumor settings [ 3 , 4 ]. (
  • Since approval of the first therapeutic monoclonal antibody (mAb) muromonab-CD3 by the United States Food and Drug Administration for treatment of organ transplant-associated acute rejections in 1992, a total of 62 mAbs have been approved by the USFDA for clinical use as of May 2016 ( 1 , 2 ). (
  • CHICAGO - Venkateshwar "Venkat" Reddy , PhD , vice president and global head of translational science for Glenmark Pharmaceuticals, spoke with HemOnc Today at ASCO Annual Meeting about the company's bispecific T-cell engager platform. (
  • Impressively, antibody fragments such as bispecific T-cell engager, bispecific killer cell engager, trispecific killer cell engager, tandem diabody, and dual-affinity-retargeting are showing exciting results in terms of recruiting and activating self-immune effector cells to target and lyse tumor cells. (
  • Here, we review the principle of a new class of bispecific antibodies called BiTE (for "bispecific T-cell engager") antibodies. (
  • This mode of action is being referred to as BiTE for "bispecific T-cell engager" technology. (
  • For example, blinatumomab, a bispecific T cell engager antibody (BiTE), has been approved for the treatment of B-cell leukemia ( 23 ). (
  • Years ago, the bispecific T-cell engager blinatumomab validated the concept of bispecific antibodies in hematology. (
  • WuXiBody™ Platform enables almost any mAb sequence pairs to be assembled into bispecific constructs. (
  • Today, dozens of next-generation bispecific antibody constructs are in clinical trials, and they are poised to have a huge impact in the treatment of lymphoma and other hematologic malignancies, experts agreed. (
  • To address this problem, bi- and trispecific antibody-like constructs have been developed. (
  • Here, we develop and characterize bispecific constructs based on well-characterized V2-glycan and V3-glycan bNAbs and show that at least one member of this class is more potent than its parental antibodies, indicating that they can simultaneously bind both of these epitopes of a single Env trimer. (
  • A particular challenge of bispecific antibody constructs that recognize the invariant CD3 signaling complex is a controlled polyclonal activation of T cells that, ideally, is exquisitely dependent on the presence of target cells. (
  • Here we analyzed 2 distinct bispecific single-chain antibody constructs of the BiTE class, called MT110 and MT103 (or MEDI-538), for conditional T-cell activation. (
  • Since the Fc region is still intact, this allows for the bsMab to trigger common immune responses when recognized by an Fc receptor, such as antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity. (
  • Antibody-dependent cell-mediated cytotoxicity, one of the most prominent modes of action of antitumor antibodies, suffers from important limitations due to the need for optimal interactions with Fcγ receptors. (
  • Bispecific antibodies have been actively studied for cancer therapy due to their potent cytotoxicity against tumor cells. (
  • A number of bispecific antibody formats have exhibited strong tumor cytotoxicity in vitro and in vivo. (
  • The purified bispecific antibody is able to trigger T cell‑mediated HER2‑specific cytotoxicity in vitro and in vivo. (
  • Trastuzumab and pertuzumab are able to directly inhibit HER2 activities and induce antibody-dependent cell-mediated cytotoxicity. (
  • Attempts to improve the cytotoxicity of antibodies, particularly in the cancer field, have led to the design of bispecific antibodies: this can occur through various strategies, such as quadroma, thioether-linked Fab' gamma fragments or genetic engineering. (
  • Bispecific antibodies capable of simultaneously binding two targets have been studied for many years with a view to their implementation in clinical practice. (
  • These days there are literally hundreds of different ways of making bispecific antibodies," says Stefan Weigand, "But few have made it into later-stage clinical trials, partly because while many of them work on paper, they are very far away from the original antibodies. (
  • Bispecific antibodies currently are in clinical trials. (
  • of bispecific antibodies in clinical trials are bringing immune cells closer to cancer targets. (
  • The clinical application of such a combined therapy with ATV-NDV vaccine cells and bi-specific antibodies allows to modify the strength of signal 1 and 2 in a quantitative and predictable way according to the immune status of the T cells and the requirements of the patients' immune system. (
  • Furthermore, Zymeworks Inc. announced the initiation of clinical development of its first product, known as ZW49, by utilizing the ZymeLink ADC platform in combination with Zymeworks' Azymetric bispecific platform. (
  • Furthermore, perspectives of bispecific antibodies in future clinical developments are addressed. (
  • Recent results from clinical studies with a CD19/CD3-bispecific BiTE antibody suggest that this therapeutic paradigm is finally showing promise for treatment of both bulky and minimal residual disease. (
  • The antibody has also obtained the IND approval from the National Medical Products Administration (NMPA) in China and will enter clinical trials in the country as well. (
  • We expect the overall clinical profile of KN046 to be superior to monotherapy with the PD-(L)1 or CTLA-4 antibody, as well as to the combination of the two antibody drugs. (
  • Almirall will further progress the antibody with the goal of taking it through clinical trials in humans and onto the market. (
  • Our bispecific antibody pipeline includes REGN1979 and a MUC16xCD3 antibody for ovarian cancer in clinical development, and a BCMAxCD3 antibody for multiple myeloma expected to enter human studies before the end of this year. (
  • In 2019, we expect to start clinical trials of a new class of bispecific antibodies that engage cellular immunity in novel ways. (
  • The Company currently has a pipeline of over 20 innovative investigative drugs for the treatment of major diseases like cancer, autoimmune diseases, inflammation and metabolic diseases, 9 of which have entered clinical stage, including two novel first-in-class bi-specific antibody drugs (PD-1/CTLA-4 and PD-1/VEGF). (
  • WuXi Biologics and ABL Bio have entered into an exclusive development and clinical manufacturing partnership for multiple bispecific antibodies. (
  • The major benefits of bispecific antibodies and the current formats used in clinical trails. (
  • Vancouver, BC, January 16, 2017--(T-Net)-- Zymeworks Inc. , a clinical-stage biopharmaceutical company dedicated to the discovery, development and commercialization of next-generation multifunctional biotherapeutics, initially focused on the treatment of cancer, today announced the successful achievement of a research milestone in a second immune-modulating bispecific antibody in its collaboration with Eli Lilly and Company ("Lilly") using Zymeworks' proprietary Azymetric™ platform. (
  • Zymeworks' lead product candidate, ZW25, is a novel bispecific antibody currently being evaluated in an adaptive Phase 1 clinical trial. (
  • Several potential therapeutic areas will be explored where inhibition of the Ang2 and VEGF pathways with this unique bispecific antibody may provide clinical benefit. (
  • Abpro will bring strong scientific, technical and clinical expertise to the new company moving forward, and its core technology platform, DiversImmune, will be used to further refine the antibody. (
  • This collaboration further validates our platform's ability to develop therapeutic antibodies against traditionally difficult targets, with compelling prospects for potential clinical utility. (
  • Boehringer Ingelheim today announced the advancement of the bi-specific and tetravalent therapeutic antibody, BI 905711, to its first-in-human clinical trial for patients with advanced gastrointestinal (GI) cancers. (
  • More than thirty years ago, not long after scientists began developing therapeutic antibodies-breakthrough medicines that precisely bind to single targets -they began thinking about the potential advantages of medicines that could hit two targets at once: bispecific antibodies. (
  • By using just one CD3-specific binding arm, such bispecific antibodies can monovalently bind to all T cells, but do so only with rather low affinity ( 7 ), which will not trigger T-cell signaling by CD3, unless the BiTE antibody is presented to the T cell in a multivalent fashion by a target cell ( 8 ). (
  • Researchers from the Ludwig Center at Johns Hopkins Medicine engineered bispecific antibodies to bind to cancer cells and recruit immune cells to the cancer cell to destroy it. (
  • CEA-TCB has a 2-to-1 binding ratio, with 1 arm of the antibody binding directly to CD3 on T cells while the remaining 2 arms simultaneously bind to CEA on the tumor. (
  • It is a bispecific antibody, based on Zymeworks' Azymetric™ platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. (
  • Among these are antibodies that bind the CD4-binding site, the V1/V2 glycan region at the Env apex, the V3-glycan epitope, the interface of the gp120 and gp41 Env subunits, the silent face (SF), and in the membrane-proximal region of gp41 ( 8 , 9 ). (
  • The XmAb 2+1 bispecific antibody format has two domains that bind the tumor target, and this bivalent binding can preferentially bind tumor cells with high target expression, potentially sparing low-expression normal tissues. (
  • According to Immune, the platform prototype bispecific antibody has been shown to retain effector functions and mediate redirect killing of target cells by cytokine induced killer T cells. (
  • Lum LG, Davol PA (2005) Retargeting T cells and immune effector cells with bispecific antibodies. (
  • We have previously developed a guide-effector bispecific system to achieve cell-type-specific signaling modulation ( 8 ). (
  • We hypothesize that internalization can be manipulated by our guide-effector-based bispecific. (
  • The BiTE® antibody construct mediated T cell-directed killing of CEA positive tumor cells within 6 hours, at low effector-to-target ratios which were independent of high concentrations of soluble CEA. (
  • The anti-CD20 x anti-CD3 trifunctional bispecific antibody (trAb) FBTA05 may improve the targeting of tumor cells by redirecting immune allogeneic effector cells while reducing the risk of undesirable reactivity against normal host cells. (
  • 2007. Antibody targeting of stem cells to infarcted myocardium. (
  • Dual-targeting antibodies may promote less toxicity by more selectively targeting the tumor reactive T cells. (
  • The bispecific antibody 9202.1/5411 lowers histamine release from RBL cells transfected with human FcεRI and human FcγRIIb and activated through human FcεRI. (
  • Antibodies developed in the laboratory to recognize more than one protein on the surface of different cells. (
  • IgG-like antibodies can be immunogenic, which means the Fc region could cause detrimental downstream immune responses caused by cells that are activated by Fc receptors. (
  • A bispecific antibody containing a 4G7 hybridoma secreting IgG1 antibody specific for B-lymphocytes and a monoclonal antibody targeting Fc gamma RI-expressing cells. (
  • One of the two arms of the antibody attaches via the CD3 receptor to the T cells. (
  • AGEN1777 is an Fc-enhancement antibody Agenus is developing to target major inhibitory receptors found on T and NK cells that seem to improve anti-tumor activity. (
  • Lu D, Zhang H, Ludwig D et al (2004) Simultaneous blockade of both the epidermal growth factor receptor and the insulin-like growth factor receptor signaling pathways in cancer cells with a fully human recombinant bispecific antibody. (
  • Behar G, Siberil S, Groulet A et al (2008) Isolation and characterization of anti--FcgammaRIII (CD16) llama single-domain antibodies that activate natural killer cells. (
  • The concept of using such bispecific antibodies to engage cytotoxic T cells for cancer cell lysis was shown by Staerz and colleagues ( 1 ). (
  • Likewise, bispecific antibodies for engagement of other cytotoxic immune cells were constructed, for instance, targeting Fcγ RI/CD64 on macrophages and Her2/neu or EGFR on tumor cells. (
  • Immune cells are not the only warriors our immune system employs to protect us against invaders like viruses, infection and cancer, antibodies are also important members of the fight. (
  • When they come into contact with a foreign invader, B cells produce antibodies and release them into the blood circulation where they can seek out and neutralize the foreign invader. (
  • CAR T-cell therapy and bispecific antibodies are two approaches that have addressed the targeting of more than one epitope, the re-directing of T lymphocytes to kill tumor cells, and the improvement of efficacy in solid tumor types. (
  • Targeted CD28 bispecific antibodies may provide conditional co-stimulation of T cells, for example, to T cells recognizing neoantigens or in concert with CD3 T-cell engaging bispecific antibodies. (
  • Xencor engineered two XmAb bispecific antibodies, B7-H3 x CD28 and PD-L1 x CD28, to provide conditional co-stimulation of T cells, activating them when bound to tumor cells. (
  • H. E. Lum, M. Miller, D. Van Epps, and L. G. Lum, Targeting Prostate Cancer Cells with T Cells Armed with Two Novel Bispecific Antibodies (OKT3 x 9187 and OKT3 x 9189) , 29th edition, 2001. (
  • As opposed to anti-CD3 bispecific antitumor antibodies, they do not engage regulatory T cells as these latter cells do not express FcγRIII. (
  • As T cells serve an important function in the killing of tumor cells (16-20), bispecific antibody that recruits T cells to kill tumor cells is of interest and has been investigated for cancer therapy (21-23). (
  • The present study reports on a T-cell engaging bispecific antibody, cluster of differentiation (CD)3-S-Fab, which targets HER2 tumor cells. (
  • Watch a time-lapse microscope video of the T-cell bispecific antibody in activating cytotoxic T lymphocytes designed to kill tumor cells. (
  • Targeting T cells to tumor cells using bispecific antibodies. (
  • Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells overexpressing the HER2 protooncogene. (
  • Recent studies have shown that human T cells can be targeted with bispecific antibody to react against human tumor cells in vitro. (
  • In additional experiments, the presence of bispecific F(ab')2 caused up to fourfold enhancement in the cytotoxic activities of human T cells against tumor cells overexpressing p185HER2 as determined by a 51Cr release assay. (
  • As a result, bispecific ADCs retained increased selectivity and mediated high tumor efficacy in EGFR and c-MET overexpressing cells whereas toxicity in primary keratinocytes as normal tissue equivalent was conjointly reduced. (
  • In vitro studies, measuring protein synthesis, showed that all three derivatives were extremely efficient at delivering saporin to L2C cells, to the extent that addition of the rabbit Fab' gamma-containing bispecific Ab to cell culture at 1 microgram/ml increased the toxicity of saporin (50% inhibiting concentration) by close to 90,000-fold. (
  • These findings have shown that bispecific F(ab' gamma)2 Ab, as well as being straightforward to prepare, can also function as an extremely efficient vector for delivering cytotoxic agents such as ribosome-inactivating protein to unwanted cells in vivo. (
  • Mosunetuzumab is basically an antibody that uses the patient's own T cells to do what a CAR T cell would do. (
  • We need more follow-up with these approaches to see tolerability and durability, but if bispecific antibodies can do what CAR T cells can do, that would be a very big advance and would represent a paradigm shift. (
  • Here the CEA and CD3 bispecific single-chain antibody MEDI-565 (also known as MT111 and AMG 211) was evaluated for its ability to activate T cells both in vitro and in vivo and to kill human tumor cell lines harboring various somatic mutations commonly found in colorectal cancers. (
  • However, treatment with such antibodies and cytotoxic antibody fusion proteins does generally not result in the induction of specific antitumor immunity and cannot prevent possible tumor recurrence if disseminated tumor cells escape cytotoxic therapy. (
  • The first-in-class BI 905711 antibody is designed to recognize both the pro-apoptotic tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAILR2) and the tumor cell anchor cadherin 17 (CDH17) to activate the self-destruction (apoptosis) pathway in co-expressing tumor cells found mostly in the GI tract. (
  • The DutaMab™ technology platform further enables the development of bi-specific antibodies on a single arm of the antibody that are characterized by a high affinity and simultaneous binding against both targets, excellent stability and good manufacturing properties. (
  • In the case of Ebola vaccines, this method allows the antibody to target intracellular targets not usually accessible by traditional monoclonal antibody treatments. (
  • The bi-specific antibodies intend to provide the next generation of targeted biologics by engaging two different targets simultaneously. (
  • For this, heavy chain repertoires from immunized transgenic rats were combined with either a randomly chosen common light chain or a light chain of an existing therapeutic antibody and screened for binders against tumor-related targets CEACAM5 and CEACAM6 by yeast surface display. (
  • Under the terms of the agreement, Zymeworks has granted Lilly a worldwide, royalty-bearing license to research, develop and commercialize certain bispecific therapeutic candidates toward Lilly's therapeutic targets. (
  • Bifunctional antibody fragment-based fusion proteins for the targeted elimination of pathogenic T-cell subsets. (
  • There are also fusion proteins mimicking the variable domains of two antibodies. (
  • Antibodies are small, Y-shaped proteins produced by a type of white blood cell called a B cell. (
  • These data show that bispecific antibody-like proteins can achieve greater neutralization potency than the bNAbs from which they were derived. (
  • Despite an extension of life expectancy associated with this treatment, resistance to EGFR tyrosine kinase inhibitors and anti-EGFR antibodies is almost inevitable. (
  • CBT plans to test two of its own candidates - a c-Met inhibitor and an anti-PD1 antibody - together with the Bossan EGFR inhibitor, which is currently in a Phase I China trial. (
  • The anti-CD3 specific single-chain antibody (green) is shared by all BiTE antibodies. (
  • The exact "ideal niche" or optimal initial and sequential treatment situation for use of a bispecific such as teclistamab, as opposed to, for example, the BCMA-targeted monoclonal antibody-drug conjugate Blenrep and anti-BCMA CAR T-cell products (such as Abecma) will be established in the real-world setting. (
  • We constructed a bispecific antibody-drug conjugate (ADC) based on the above bispecific design and found that the bispecific ADC is more potent than monospecific ADCs in tumor cell killing both in vitro and in vivo . (
  • Antibody-drug conjugate (ADC) is a class of targeted therapeutic that has shown effectiveness in the clinic ( 1, 2 ). (
  • In order to improve the therapeutic effect of antibodies, a number of approaches have been studied, including antibody conjugate TDM1 ( 15 ). (
  • Tumor pretargeting is obtained by using a bispecific monoclonal antibody [BsmAb, anti-CEA × anti-DTPA-indium complex (DTPA-In)] and pegylated radioactive liposomes containing a lipid-hapten conjugate (DSPE-PEG-DTPA-In). (
  • A number of studies of mosunetuzumab are ongoing in lymphoma and other B-cell malignancies, including phase Ib/II studies in NHL as monotherapy and in combination with other drug regimens used to treat NHL, such as R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone), CHP (cyclophosphamide, doxorubicin, prednisone), or the antibody-drug conjugate polatuzumab vedotin. (
  • Supported by rapid advances in antibody engineering and the development of several technological platforms such as Triomab or bispecific T cell engagers (BiTEs), the "bispecifics" market has increased significantly over the past decade and may occupy a pivotal space in the future. (
  • With multiple in-house proprietary platforms including bispecifics, protein engineering and antibody screening, Alphamab Oncology has built a robust pipeline in oncology/immunology. (
  • Under the terms of the agreement, Almirall has access to WuXi Biologics' proprietary antibody platforms including WuXiBody™ to discover multiple novel bispecific antibodies. (
  • It can effectively break through the CMC barriers for many bispecific antibodies development with high expression yield, high stability, good solubility, and easy purification to homogeneity, expedite the process by 6-18 months and significantly reduce manufacturing cost, a limitation still facing by many other current bispecific platforms. (
  • BeiGene will acquire Asian rights to two bispecific antibodies from Zymeworks and will have rights to three to-be-discovered bispecific candidates developed by Zymeworks platforms. (
  • Being natural mitigates many problems with traditional bispecific antibody platforms, including immunogenicity risks, developability issues and mass production difficulties. (
  • 2014. A novel platform for engineering blood-brain barrier-crossing bispecific biologics. (
  • The agreement showcases the expansive biologics pipeline of ABL Bio and the world leading technical expertise and capabilities of WuXi Biologics in developing bispecific programs. (
  • The partnership with WuXi Biologics is an important strategy for growing our internal and external programs of next-generation of biologics such as bispecific antibody. (
  • I believe that the partnership with WuXi Biologics will bring a synergy effect for developing our bispecific antibody pipelines and help us step up to be a global top-tier biotechnology company for immuno-oncology and neurodegenerative disease treatment. (
  • WuXi Biologics has been well recognized as a global leader in the development and manufacturing of difficult biologics such as bispecific antibodies. (
  • WuXiBody™ is a leading proprietary bispecific antibody platform developed by WuXi Biologics. (
  • To address these limitations, bi- and multispecific antibody-like biologics of various architectures have been developed ( 20 - 23 ). (
  • Genedata, a leading provider of advanced software solutions for drug discovery and life science research, has announced the release of Genedata Biologics™ 4.0, the latest version of its enterprise workflow support and data management solution for biologics R&D. This major new release provides novel tools for systematically designing, cloning, expressing, purifying, and testing bi- and multi-specific antibodies. (
  • Genedata Biologics 4.0 enables standardized processing and assessment of next-generation antibody formats (e.g. (
  • Here, we describe a new class of bispecific antibodies targeting the V2-glycan (apex) and V3-glycan regions of the HIV-1 envelope glycoprotein (Env). (
  • Xencor has expanded its T-cell redirecting CD3 class of bispecific antibodies to create an XmAb 2+1 bispecific antibody format, utilizing an engineered heterodimeric Fc domain, two identical tumor targeting domains and one CD3 targeting domain. (
  • The present review describes the main formats of bispecific antibodies, methods for their generation, and possibilities for practical application. (
  • Over 50 different formats of bispecific antibodies are now available for therapeutic and diagnostic applications [ 2 ]. (
  • The researchers adapted this technology into a two-part strategy that consists first of small-scale generation of bispecific antibodies lacking a common light chain and hinge disulfides to facilitate proof-of-concept studies, followed by the identification of a common light chain-bispecific antibody for large-scale production with high purity and yield. (
  • Especially, recent development of IgG-fusions with disulfide-stabilized Fv fragments and of CrossMab-technologies facilitates the generation of bispecific antibodies with IgG-like architectures. (
  • In an important first step to simplifying the production of bispecific antibodies, in 1997 Genentech scientist Paul Carter was the main inventor of the "knobs-and-holes" technology that solved the problem of the two heavy chains being paired correctly. (
  • However, effective production of bispecific antibodies remains challenging for the majority of bispecific antibody formats. (
  • 2015. Phase 1 study of a bispecific ligand-directed toxin targeting CD22 and CD19 (DT2219) for refractory B-cell malignancies. (
  • These engineered antibodies typically have greater breadth than the native bNAbs from which they were derived, but they are not more potent because they do not, in most cases, simultaneously engage more than a single epitope of the HIV-1 envelope glycoprotein (Env). (
  • Moreover, these bispecific antibodies are markedly more potent than their parental bNAbs, likely because they simultaneously engage both the apex and V3-glycan epitopes of Env. (
  • For the first time in diabetic macular edema, a clinically meaningful and statistically significant improvement in visual acuity compared to anti-VEGF alone has been demonstrated by simultaneously neutralising both angiopoietin-2 and VEGF-A with a bispecific antibody," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. (
  • Unique biological and pharmacological properties, as well as the diversity of their formats, make it possible to consider bispecific antibodies as promising agents for use in various procedures: from visualization of intracellular processes to targeted anticancer therapy. (
  • Genentech is exploring the potential of combining T-cell bispecific antibodies with other anticancer therapies, including PD-L1 inhibitors and antibody drug conjugates in the pursuit of enhancing T-cell-mediated cancer immunity. (
  • This is the key issue that delayed the entire field of bispecific antibodies for years," says Janice Reichert, Executive Director of the Antibody Society. (
  • Removab, the first therapeutic antibody drug in the field of bispecific antibodies who was approved by the European Union on April 20, 2009, is certain to be First-in-Class consisting by antibody-peptide . (
  • Genetic engineering has resulted in more than 50 recombinant bispecific antibody formats over the past two decades. (
  • Here, newly engineered bispecific and multispecific antibodies will be put to the test. (
  • In the past decade, many novel concepts to generate bispecific and multispecific antibodies have evolved successfully into a range of formats from full bispecific immunoglobulin gammas to antibody fragments. (
  • The use of CrossMAb technology for the generation of bi- and multispecific antibodies. (
  • Antibody fragments can be advantageous for particular downstream applications due to improved thermostability, solubility and diffusion compared to a full-length mAbs. (
  • Ideally, a potent cytotoxic attached to a cell-type-specific antibody can route the cytotoxic to the target cell and preferentially accumulate in the target tissue. (
  • The past decade has seen the emergence of a number of potent broadly neutralizing antibodies (bNAbs) that recognize nearly every available surface of the HIV-1 envelope glycoprotein (Env) ( 1 - 7 ). (
  • Although they are more potent and much broader than previously described HIV-1 neutralizing antibodies, the high HIV-1 mutation rate and preexisting diversity of Env in infected persons precludes their use as monotherapy ( 10 - 19 ). (
  • Scientists at MedImmune leveraged the company's significant experience with bispecific antibody development, engineering a novel bispecific antibody that demonstrated potent activity in animal models, which may be useful in targeting disease indications with high unmet needs. (
  • Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. (
  • But despite promising results, RIT is not as successful against solid malignancies, which are usually more radioresistant and less accessible to radiolabeled antibodies ( 3 ). (
  • A flexible bispecific antibody (bsMAb) multistep, pretargeting system that potentially can be developed for use with a variety of different imaging or therapeutic agents is described herein. (
  • BiTE antibodies consistently show a high potency of redirected lysis in vitro , and high antitumor activity in various animal models. (
  • In vitro, both bispecific antibodies exhibited highly selective blocking of TGFβ activity in PD-1-high and CD5-high T cell populations. (
  • Altogether, the described strategy represents a combination of in vivo immunization with an in vitro selection method, which allows for the integration of existing therapeutic antibodies into a bispecific format. (
  • Bispecific antibodies have been extensively studied in vitro and in vivo for their use in redirected tumor cell lysis. (
  • Lu D, Zhang H, Koo H et al (2005) A fully human recombinant IgG-like bispecific antibody to both the epidermal growth factor receptor and the insulin-like growth factor receptor for enhanced antitumor activity. (
  • Genentech is exploring the potential of two innovative T-cell bispecific antibody structures to reinitiate an antitumor immune response across multiple tumor types. (
  • Therefore, bispecific antibodies may be used to promote antitumor immune activity, while bypassing steps in the cancer immunity cycle . (
  • Azymetric™ bispecifics can also be engineered to enhance internalization of the antibody into the tumor cell and consequently increase the delivery of cytotoxic payloads. (
  • Multistep targeting systems represent highly selective alternatives to targeting systems using directly radiolabeled antibodies for diagnostic and therapeutic applications. (
  • However, the possibility of using this radionuclide with a directly radiolabeled antibody for RIT is limited by its short physical half-life and the specific activities obtained during direct radiolabeling of antibodies (70-80 MBq/nmol) ( 7 - 9 ) as well as slow tumor uptake ( 11 , 12 ). (
  • As evidenced by the recent approvals of Removab (EU, Trion Pharma) in 2009 and of Blincyto (US, Amgen) in 2014, the high potential of bispecific antibodies in the field of immuno-oncology is eliciting a renewed interest from pharmaceutical companies. (
  • Alphamab has developed in house the next-generation immune-oncology program KN046, a bispecific antibody targeting both PD-L1 and CTLA-4. (
  • Data from Zymeworks' ongoing multi-center Phase 1 study showed single agent ZW25, a bispecific antibody, induced anti-tumor activity and was well tolerated in heavily pretreated patients with a variety of HER2-expressing cancers. (
  • In December 2014, we announced the acquisition of Dutalys to strengthen our capabilities in the discovery and development of fully human, bi-specific antibodies based on their proprietary DutaMabs™ technology. (
  • While there are many in various phases of development, only three bispecific medicines have been approved worldwide, one of which was later withdrawn from the market. (
  • According to the RNCOS report entitled "Global Bi-Specific Antibodies Market Forecast to 2022" , since the last few years, numerous companies have started showing interest in the development bi-specific antibodies. (
  • Increasing application of bi-specific antibodies in drug development is expected to further increase the revenues of the key players in Global Bi-Specific Antibodies Market. (
  • Further progress in the development of bispecific antibodies came from reduction of antibodies to their minimal binding domains. (
  • The successful development of antibody drugs against immune checkpoints marked a major breakthrough in the history of anti-cancer research. (
  • The Fast Track Designation of AK104 is another significant milestone in the development of this innovative bispecific antibody. (
  • The Company is a biopharmaceutical company dedicated to the research, development, manufacturing and commercialization of innovative antibody drugs that are affordable to patients worldwide. (
  • Since the Company's establishment, the Company has established an comprehensive end-to-end drug development platform (ACE Platform) and system, encompassing fully integrated drug discovery and development functions, including target validation, antibody drug discovery and development, CMC process development, and GMP-compliant commercial scale manufacturing. (
  • The Company has also successfully established a bi-specific antibody drug development technology (Tetrabody technology). (
  • Our XmAb bispecific Fc domains were specifically created to enable the rapid design and simplified development of a wide range of multi-specific antibodies and other protein structures, such as our engineered cytokines," said John Desjarlais, Ph.D., senior vice president and chief scientific officer at Xencor. (
  • The flexibility of this system is based on use of an antibody directed against histamine-succinyl-glycine (HSG) and the development of peptides containing the HSG residue. (
  • Cell-type-specific intracellular payload delivery is desired for antibody-based-targeted therapy development. (
  • Although progresses have been slowed by technical constraints, there is little doubt that this class of novel antibodies derivatives will experience a promising development. (
  • 2-4 Genentech is exploring this approach through the development of T-cell bispecific antibodies-a new generation of biologically engineered antibodies. (
  • Azymetric™ bispecific technology enables the development of biotherapeutics with dual-targeting of receptors/ligands and simultaneous blockade of multiple signaling pathways, increasing tumor-specific targeting and efficacy while reducing toxicities and the potential for drug-resistance. (
  • GenScript Biotech Corporation, a world leading bio-pharmaceutical CDMO company, has entered into an exclusive strategic drug development cooperation with REMD Biotherapeutics Inc. (hereinafter REMD) on several bispecific antibodies. (
  • GenScript will help REMD with candidate bispecific antibody drug development and provide a variety of technical support and services. (
  • We are glad to enter into a strategic cooperation with GenScript on bispecific antibody drugs," said Dr. Hai Yan, co-founder and CEO of REMD, "At REMD, we focus on the development of novel antibody drugs. (
  • Our cooperation with GenScript allows us to join forces, which will bring us GenScript's platform and experience in antibody drug research and development and expand our novel antibody drug pipelines. (
  • With further study, mosunetuzumab, and perhaps other bispecific antibodies in development, may become an option after CAR T-cell therapy for patients with B-cell lymphomas and leukemias who no longer have treatment options. (
  • Other bispecific antibodies are under development, and early studies of some of these agents also were presented at the ASH meeting. (
  • Through its core technology, the DiversImmune[TM] platform, Abpro leverages synthetic biology and immunology to accelerate antibody discovery and development in the life sciences industry. (
  • The global Bispecific Antibody market report is a comprehensive research that focuses on the overall consumption structure, development trends, sales models and sales of top countries in the global Bispecific Antibody market. (
  • Bispecific antibodies recognize two different epitopes. (
  • Immune Pharmaceuticals said today it has agreed to exclusively license from Atlante Biotech the patents and know-how for a new format of bispecific antibodies. (
  • Our research will focus on the application of this novel bispecific platform to target immune checkpoints. (
  • A collaborative European consortium led by Jean Kadouche, Ph.D., a scientific co-founder of Immune now with Atlante Biotech, developed the novel platform for production of tetravalent IgG1-like bispecific antibodies. (
  • Experiments to define the optimal treatment regimen in this model showed that, although the administration of saporin and bispecific Ab at separate sites could be therapeutically effective, mixing the Ab and saporin to form immune complexes before injection did generally enhance their performance. (
  • HONG KONG - China's Suzhou Alphamab Co. Ltd. has obtained the IND approval from regulators for its HER2 bispecific antibody, KN-026. (
  • In another example, a bispecific composed of a moderately internalizing antibody arm (anti-HER2) and an internalization-inducing antibody arm (anti-CD63, anti-PRLR, or anti-APLP2) was constructed and used to improve ADC uptake ( 5-7 ). (
  • However, despite those efforts, the bispecific ADC only showed limited improvement over the parental monospecific anti-HER2 ADC, suggesting that key parameters regarding this design remains to be delineated. (
  • The two antibodies may increase the survival time when combined with chemotherapy in patients with HER2-overexpressing breast cancer (10-12). (
  • Numerous bispecific antibodies targeting different tumor biomarkers, including HER2, have also been reported (24-27). (
  • A combination of B7-H3 x CD28 and a B7-H3 x CD3 bispecific antibody enhanced anti-tumor activity compared to either bispecific antibody alone in an in vivo model of breast cancer. (
  • Xencor engineered two XmAb bispecific antibodies, PD-1 x TGFβR2 and CD5 x TGFβR2, to selectively block the suppressive activity of TGFβ on specific T-cell populations and to enhance their anti-tumor activity while avoiding the toxicity associated with systemic blockade. (
  • Anti-tumor activity was enhanced when combined with an anti-PD-1 antibody, compared to anti-PD-1 alone or an anti-PD-L1/TGFβ trap. (
  • Anti-tumor activity was enhanced when combined with an anti-PD-1 antibody. (
  • NOIDA, India - April 4, 2018 - PRLog -- Bi-specific antibody is one of the most potentially powerful tools which have emerged in the biopharmaceutical industry. (
  • This new compact, linker-free bispecific antibody format offers a promising approach for optimizing antibody-based therapies. (
  • CAR T-cell therapies are here to stay, but the question is whether bispecific antibodies will encroach on them," he commented. (
  • The second part of the presentation will focus on the characterization of a bispecific antibody fusion protein in different formulations, and how DLS-based formulation ranking correlates with the ranking based on aggregates formed after long-term storage. (
AbbVie, Harpoon expand bispecific antibody pact