Antibodies, Bispecific: 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.Antibodies: 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).Antibody Specificity: 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, Monoclonal: Antibodies produced by a single clone of cells.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Single-Chain Antibodies: 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.Antibody Affinity: 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.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Antibodies, Neutralizing: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.Binding Sites, Antibody: 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, Anti-Idiotypic: Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.Antigens, CD3: 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).Immunoglobulin Fragments: Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques.Fluorescent Antibody Technique: 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.Antibodies, Neoplasm: Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.Haptens: 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.Immunoglobulin Fab Fragments: 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.Epitopes: Sites on an antigen that interact with specific antibodies.HIV Antibodies: Antibodies reactive with HIV ANTIGENS.Antibodies, Protozoan: Immunoglobulins produced in a response to PROTOZOAN ANTIGENS.Antibody-Dependent Cell Cytotoxicity: 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.Antibodies, Antinuclear: 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.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Radioimmunotherapy: 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).Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Hybridomas: 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.Radioimmunodetection: 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.Immunotherapy: 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.Molecular Sequence Data: 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.Immunotoxins: 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.Receptors, IgG: 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).Mice, Inbred BALB CAntigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Pentetic Acid: An iron chelating agent with properties like EDETIC ACID. DTPA has also been used as a chelator for other metals, such as plutonium.Antigens, CD19: Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.Amino Acid Sequence: 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.Protein Engineering: 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.Sialic Acid Binding Ig-like Lectin 2: A lectin and cell adhesion molecule found in B-LYMPHOCYTES. It interacts with SIALIC ACIDS and mediates signaling from B-CELL ANTIGEN RECEPTORS.Immunoglobulin M: 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.Antigens, Neoplasm: 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.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Antibodies, Fungal: Immunoglobulins produced in a response to FUNGAL ANTIGENS.Carcinoembryonic Antigen: 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.Single-Domain Antibodies: An immunoglobulin fragment composed of one variable domain from an IMMUNOGLOBULIN HEAVY CHAIN or IMMUNOGLOBULIN LIGHT CHAIN.Antigen-Antibody Complex: 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.Immunoglobulin Variable Region: 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.Neutralization Tests: 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).T-Lymphocytes: 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.Cytotoxicity, Immunologic: 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.Antigens, CD20: 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.Indium Radioisotopes: 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, Monoclonal, Humanized: 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.Enzyme-Linked Immunosorbent Assay: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Tumor Cells, Cultured: 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, Blocking: 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 Fusion Proteins: 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.Immunization, Passive: Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).Cell Line: Established cell cultures that have the potential to propagate indefinitely.Mice, Nude: 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, Heterophile: 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, Catalytic: Antibodies that can catalyze a wide variety of chemical reactions. They are characterized by high substrate specificity and share many mechanistic features with enzymes.Rabbits: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Lymphocyte Activation: 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.Immunoglobulin Fc Fragments: 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.Leukemia, B-Cell: A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.Tissue Distribution: 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.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Iodine Radioisotopes: 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, SCID: 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.Immunization: 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).Lymphoma, B-Cell: A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Antigens, CD: 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.Flow Cytometry: 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.Heterocyclic Compounds, 1-Ring: 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.Immunoglobulin A: 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.Fluorescent Antibody Technique, Indirect: 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)Immune Sera: 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.Blotting, Western: 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.Peptide Library: 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.Epitope Mapping: 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.Antibodies, Antiphospholipid: 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, Cultured: 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.Xenograft Model Antitumor Assays: 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, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Neoplasms: 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.B-Lymphocytes: 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.Receptors, Fc: 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.Immunoenzyme Techniques: 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.Immunoglobulin Heavy Chains: 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, Heterologous: Transplantation between animals of different species.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Antigens, Surface: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Immunoglobulin Light Chains: 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.Protein Binding: 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.Immunoassay: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Binding, Competitive: 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.Muromonab-CD3: 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, Differentiation, T-Lymphocyte: 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.Molecular Weight: The sum of the weight of all the atoms in a molecule.Antibodies, Monoclonal, Murine-Derived: Antibodies obtained from a single clone of cells grown in mice or rats.Immunoglobulins: 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.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Immunoblotting: 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.Radioimmunoassay: 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.Cell Adhesion Molecules: 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.Complement System Proteins: 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).Cloning, Molecular: 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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Immunoconjugates: 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.Sensitivity and Specificity: 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)Complement Fixation Tests: 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.Receptor, erbB-2: 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.Antigens, Tumor-Associated, Carbohydrate: 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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Hemagglutination Tests: Sensitive tests to measure certain antigens, antibodies, or viruses, using their ability to agglutinate certain erythrocytes. (From Stedman, 26th ed)Hemagglutination Inhibition Tests: 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.Genetic Vectors: 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.Antibodies, Antineutrophil Cytoplasmic: 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.Peptides: 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.Seroepidemiologic Studies: 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.Mice, Inbred C57BLReceptor, Epidermal Growth Factor: 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.Immunoglobulin Idiotypes: 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.Immunologic Techniques: Techniques used to demonstrate or measure an immune response, and to identify or measure antigens using antibodies.Chromatography, Affinity: 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)Antigens, Differentiation, B-Lymphocyte: Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.Ribosome Inactivating Proteins, Type 1: Ribosome inactivating proteins consisting of only the toxic A subunit, which is a polypeptide of around 30 kDa.Escherichia coli: 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.Immunosorbent Techniques: Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.Killer Cells, Lymphokine-Activated: 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.Camels: Hoofed mammals with four legs, a big-lipped snout, and a humped back belonging to the family Camelidae.Spleen: An encapsulated lymphatic organ through which venous blood filters.Kinetics: 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
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 ...
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 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 ...
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)
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 ...
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...
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.
cansSAR 3D Structure of 6BA5_P | POTENT AND SELECTIVE ANTITUMOR ACTIVITY OF A T-CELL ENGAGING BISPECIFIC ANTIBODY TARGETING A MEMBRANE-PROXIMAL EPITOPE OF ROR1 | 6BA5
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.
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
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 www.biteantibodies.com.. 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 ...
Antibody fragments, especially single-chain Fv fragments, have been established for the generation of immunoliposomes for targeted drug delivery in cancer therapy and other applications. Bispecific immunoliposomes should be useful for dual targeting addressing inter- and intratumoral heterogeneity of tumor antigen expression. Here, we established a protocol to generate dual-targeted immunoliposomes using genetically engineered scFv molecules recognizing two different tumor-associated antigens, EGFR and CEA (CEACAM5), applying a step-wise insertion of antibody-coupled micelles into preformed PEGylated liposomes. The dual-targeted immunoliposomes retained binding activity for both antigens and combined the selectivity of both antibodies within one liposome. Thus, these dual-targeted immunoliposomes should be suitable to deliver therapeutic payloads to tumor cells expressing EGFR or CEA, or both antigens.
The insulin-like growth factor 2 (IGF2) is an important target for cancer therapy. We have previously proposed an approach for fast and irreversible removal of IGF2 from the circulation by using monoclonal antibodies (mAbs) that bind to two or more non-overlapping epitopes on the same molecule. We provided initial evidence for the formation of oligomeric antibody-ligand complexes that can bind to cells expressing Fc gamma receptors (FcγRs) with high avidity using an antibody domain with relatively low affinity as one of the anti-IGF2 mAbs. Recently, we identified a mAb, m708.5, in a scFv format which binds to both IGF2 and IGF1 with very high (pM) affinity. Interestingly, and rather surprisingly, this mAb did not compete with our other high affinity mAb, m610.27, for binding to IGF2. Therefore, we generated a new bispecific mAb, m67, by combining m708.5 and m610.27. As expected m67 potently inhibited binding of IGF2 to cells expressing the IGF1R and its phosphorylation, and resulted in ...
The present invention utilizes two monoclonal antibodies, 679 and hMN14, and two point mutations of 679, (679-VH (I3Q) and 679-VK(C101S)), to produce antigen specific diabodies. In addition, a bispecific diabody is produced from hMN14 and h679, which is obtained by grafting the CDRs of 679 onto a framework of amino acid residues found in human antibodies. The murine monoclonal antibody designated 679 (an IgGl, K) binds with high affinity to molecules containing the moiety histamine-succinyl-glycyl (HSG) (Morel etal, Molecular Immunology, 22, 995-1000, 1990). The nucleotide sequence pertaining to the variable domains (VH and VK) of 679 has been determined (Qu et al., unpublished results). VK is one of two isotypes of the antibody light chains, Vu As depicted in Figure 1, the design of the gene construct (679-scFv-L5) for expressing a 679 diabody possesses the following features: 1) The carboxyl terminal end of VH is linked to the amino terminal end of VK by the peptide linker Gly-Gly-Gly-Gly-Ser ...
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Covagen (a Cilag GmbH International company) is developing bi- and trispecific antibodies, FynomAbs®, for the treatment of inflammation and cancer. The company
SAN DIEGO--(BUSINESS WIRE)-- Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) today announced that it has entered into a commercial license and supply agreement with Amgen, granting rights to use Ligands Captisol technology in the formulation of AMG 330. Captisol is a patent protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. AMG 330 is an anti-CD33 x anti-CD3 (BiTE®) bispecific antibody construct. It is being investigated as a treatment for acute myeloid leukemia by Amgen. This license agreement replaces the prior research agreement which allowed Amgen to evaluate AMG 330 with Captisol in preclinical and early clinical studies. Under this new commercial license agreement, Amgen receives exclusive worldwide rights to combine Captisol with AMG 330 for use in humans for a wide variety of therapeutic indications. In addition to an upfront payment, Ligand is entitled to potential milestone payments, royalties and revenue from ...
Class: Biological Therapy. Generic Name: Blinatumomab. Trade Name: Blincyto®. For which conditions is this drug approved? Blincyto is approved for treatment of a certain type of acute lymphoblastic leukemia (ALL): Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute ALL.. What is the mechanism of action? Blincyto is a type of drug known as a monoclonal antibody. Monoclonal antibodies target and attach to cancer cells, which tells the immune system to destroy the cancer. Specifically, Blincyto targets a protein called CD19 thats found on the surface of B-cell leukemia cells. Another protein, CD3, thats found on the surface of T-cell lymphocytes (part of the immune system), then connects with CD19 to destroy the cancer cells.. How is Blincyto typically given (administered)? Blincyto is given by intravenous (IV) infusion into your vein using an infusion pump. One treatment cycle includes a continuous IV infusion for four weeks, followed by a two-week break during which ...
Follow-Up Data Presented at the American Society of Hematology (ASH) Annual Meeting Indicates that Blinatumomab is Able to Induce Durable Remission in Patients with Relapsed NHL
This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute
PRIMARY OBJECTIVES:I. To compare the overall survival (OS) of blinatumomab in conjunction with chemotherapy to chemotherapy alone in patients with
A novel paradigm in tumor biology suggests that non-small cell lung cancer (NSCLC) growth is driven by lung cancer stem cell-like cells (LCSCs), but here are still not any effective strategies to remove LCSCs. The bispecific antibody is a novel antibody, which can target two different antigens and mediate specific killing effects by selectively redirecting effector cells to the target cells. Here, we designed and synthesized a new bispecific antibody (BsAb), BsAb-5, that can target cellular-mesenchymal to epithelial transition factor (c-MET) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) in CD166+ LCSCs with high affinity and specificity, for the first time ...
Clinical trial for childhood ALL | leukemia , Hyper-CVAD Regimen in Sequential Combination With Blinatumomab as Frontline Therapy for Adults With B-Cell Lineage Acute Lymphocytic Leukemia
BLINCYTO (Blinatumomab) drug information & product resources from MPR including dosage information, educational materials, & patient assistance.
THOUSAND OAKS, Calif., Oct. 3, 2016 /PRNewswire/ -- Study Results Published In Journal of Clinical Oncology Show BLINCYTO® (blinatumomab) Induced Complete...
Therapeutic antibody drugs have recently experienced explosive growth due in large part to the fact that immunotherapies stimulate the immune system to attack cancer cells.
PROTEINFRAGMENTE (BIOTECHNOLOGIE); ANTIKÖRPER + IMMUNOGLOBULINE + GAMMAGLOBULINE (IMMUNOLOGIE); ESCHERICHIA (MIKROBIOLOGIE); PROTEIN FRAGMENTS (BIOTECHNOLOGY); ANTIBODIES + IMMUNOGLOBULINS + GAMMA GLOBULINS (IMMUNOLOGY); ESCHERICHIA (MICROBIOLOGY ...
The Science paper gave two bits of useful information on this subject. First, they actually measured the release of cytokines by their treatment and second they have demonstrated that giving high doses of steroids does not detract from the killing ability of the bispecific antibody. In fact patients were given methylprednisolone and low molecular weight heparin during the first treatment days as prophylaxis against cytokine release problems. The side effects of the treatment were mostly well managed. One patient with a history of near fatal sepsis died after developing an infection on this treatment. Another patient with hypogammaglobulinemia had treatment discontinued because of the development of pneumonia. One patient with a history of renal insufficiency had the drug stopped because of metabolic acidosis accompanied by a seizure. Five patients had the drug stopped because of CNS-related events; two with confusion, two with cerebellar symptoms and one with the seizure already alluded to. Al ...
Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from two Phase I studies evaluating the novel cancer immunotherapy CEA-TCB (RO6958688; RG7802), a molecule that binds T-cells and tumour cells simultaneously. CEA-TCB was studied in patients with carcinoembryonic antigen (CEA)-positive solid tumours, including microsatellite stable (MSS) metastatic colorectal cancers (mCRC) that overexpress CEA and progressed after at least two prior chemotherapy regimens.1 The studies demonstrated encouraging anti-tumour activity of CEA-TCB as a monotherapy, which was further enhanced in combination with TECENTRIQ® (atezolizumab). In the monotherapy, out of 31 patients with mCRC treated with CEA-TCB doses of 60mg or above, 14 patients (45%) showed either partial response (n=2, 6%) or stable disease (n=12, 39%). For the combination, of 25 patients treated with doses of 5-160mg of CEA-TCB, 11 patients with MSS mCRC were treated at doses shown to induce tumour lesion inflammation (80 and 160 mg). Nine of ...
BISPECIFIC ANTIBODIES AGAINST CD3 EPSILON AND BCMA FOR USE IN TREATMENT OF DISEASES | BISPECIFIC ANTIBODIES AGAINST CD3EPSILON AND BCMA | ANTI-CEACAM1 RECOMBINANT ANTIBODIES FOR CANCER THERAPY | METHODS OF CONSTRUCTING AMINO TERMINAL IMMUNOGLOBULIN FUSION PROTEINS AND COMPOSITIONS THEREOF | ANTI P2X7 RECEPTOR ANTIBODIES AND FRAGMENTS THEREOF |
A bispecific antibody can bind two different antigens. Immunoglobulin G (IgG) type antibodies have two binding sites with different variable regions. An IgG variable region is made up of a variable light-chain sequence (VL) and a variable heavy-chain sequence (VH). The light chains (LCs) of common LC antibodies are identical for both variable regions, leaving the heavy chain (HC) for generating different specificities. Thus, recombinant host cells for production of common LC bispecific antibodies carry genes for both HCs, with…. ...
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The CD3 antigen is a protein complex composed of four distinct chains: CD3γ chain, CD3δ chain, and two CD3ε chains. These chains are highly homologous cell surface proteins that are members of the immunoglobulin superfamily and contain a single extracellular immunoglobulin domain. The transmembrane region of these CD3 chains is negatively charged, allowing them to associate with the positively charged T cell antigen receptor (TCR) chains (TCRα and TCRβ). The intracellular tails of the CD3 chains contain a single conserved motif, known as an immunoreceptor tyrosine-based activation motif (ITAM) which is essential for the signaling capacity of the TCR. Association of the CD3 chains with TCR and the ζ-chain (accessory molecules of TCR) generates an activation signal in T lymphocytes. Thus, the TCR complex is composed of the TCR, zeta-chain, and CD3 molecules ...
Abstract. During the last decade, the development of improved and novel approaches for the treatment of hemophilia A has expanded tremendously. These approache
We described the development and characterization of REGN4018, a human full-length bispecific antibody that targets CD3 and the tumor antigen MUC16. REGN4018 could induce potent cytotoxicity in vitro against MUC16-expressing cells and was not hampered by excess amounts of CA-125, which may be present in patients with ovarian cancer.. The characterization of immuno-oncology clinical candidates is often carried out in immunodeficient mice with engrafted human immune cells. These models can be valuable in demonstrating potency, and indeed, we demonstrated efficacy of REGN4018 in such a model with OVCAR-3 cells. However, immunodeficient models have some limitations. For example, the activation status and proliferation rate of human T cells transferred to an immunodeficient xenogenic mouse may be considerably different to those in an autologous immunocompetent environment. Furthermore, these models do not express human MUC16 in nontumor (normal) tissues and thus do not allow for assessment of effects ...
In this study we adopted the guide-effector bispecific antibody design that we developed previously for cell-type-specific signaling modulation (8), and achieved cell-type-specific modulation of internalization. We show that when the guide-to-effector ratio crosses over a threshold (in our EphA2/ALCAM example, 1:5), a noninternalizing antigen (ALCAM) can be rendered internalizing by the bispecific. When the guide-to-effector ratio falls below the threshold, an internalizing antigen (EphA2) can be rendered non- or slowly internalizing by the bispecific. Thus in the context of bispecific targeting, the internalization behavior of a cell surface antigen is significantly impacted by its neighboring antigens, and can be readily manipulated in either direction through bispecific-based targeting of appropriately selected guide/effector pairs.. Our study has relevance to therapeutic development. In the direction of converting a noninternalizing into an internalizing antigen, our study has direct ...
Shareholders and interested parties are invited to participate in the conference call hosted by www.biotechstocks.com. The call will start promptly at 4:15pm EST on Wednesday, August 16, 2017. The dial in number for the call is 712-775-7031. Meeting ID number is 576-591-822.. About GT Biopharma, Inc.: GT Biopharma, Inc (formerly known as Oxis International, Inc.) is an immuno-oncology focused company developing innovative drugs focused on the treatment of cancer and other unmet medical needs. Oxis lead drug candidate, OXS-1550 (DT2219ARL) is a novel bispecific scFv recombinant fusion protein-drug conjugate composed of the variable regions of the heavy and light chains of anti-CD19 and anti-CD22 antibodies and a modified form of diphtheria toxin as its cytotoxic drug payload. OXS-1550 targets cancer cells expressing the CD19 receptor or CD22 receptor or both receptors. When OXS-1550 binds to cancer cells, the cancer cells internalize the drug and are killed due to the action of drugs cytotoxic ...
... - An FDA oncology analysis of CD3 bispecific constructs and first-in-human .. The following information was collected for each IND from FDA/. Introduction.
The speaker for our June 8, 2019 meeting will be Adam Cohen, MD, Penn Medicine. Dr. Cohen will give us an overview of immunotherapy and its role in the treatment of multiple myeloma. As you probably know, there has been tremendous progress recently in the use immunotherapy to treat many forms of cancer, including multiple myeloma. ...
Free Online Library: 3SBio Signs Exclusive Patent License Agreement for DIG-KT, a Bi-Specific mAb targeting VEGFR2 and Tie-2 with PharmAbcine. by PR Newswire; Business News, opinion and commentary Biological products Licensing agreements Vascular endothelial growth factor
Micromet, Inc. has announced that the Paul-Ehrlich Institute, Langen, Germany, has approved an Investigational Medicinal Product Dossier for the conduct of a phase II clinical trial testing MT103 in patients with acute lymphoblastic leukemia. 1
The invention relates to bispecific tetravalent receptors of the formula I ##STR1## or formula II ##STR2## against a tumor-associated antigen and against an agent active against tumors.
Elsässer D, Valerius T, Repp R, Weiner GJ, Deo Y, Kalden JR, van de Winkel JG, Stevenson GT, Glennie MJ, Gramatzki M. HLA class II as potential target antigen on malignant B cells for therapy with bispecific antibodies in combination with granulocyte colony-stimulating factor. Blood. 1996 May 1;87(9):3803-12. PMID:8611706 Note on publication: Describes the preparation and characterisation of anti human HLA class II antibody by of ADCC of G-CSF primed PMN expressing in the presence of F3.3 to HLA class II related epitope (HLA-DR). Reviews: No reviews available for this antibody yet. Be the first to submit a review at pAbmAbs and enter into their monthly prize draw ...
A high number of therapeutic antibodies and their derivates e.g. antibody-drug conjugates (ADC) are under preclinical or clinical evaluation for the treatment of cancer. Most of those ADCs are based on the IgG1 or IgG4 subtype, depending on whether additional effector functions are desired or not. In contrast to IgG1, IgG4 is hardly capable to induce antibody-dependent cell-mediated or complement-dependent cytotoxicity and thus IgG4-based ADCs with cytotoxic payloads targeting only proliferating cells may have a preferred safety profile. Another unique property of the IgG4 subtype is the in vivo exchange of half-antibodies, resulting in random bispecific antibodies. BT062 (indatuximab ravtansine) is an ADC composed of an anti-CD138 IgG4 antibody conjugated to the highly cytotoxic maytansin derivate DM4. BT062 is currently evaluated in a clinical trial for the treatment of multiple myeloma. To investigate the influence of IgG4 half-antibody exchange on the functional properties and efficacy of ...
Celgene and Adimab form partnership to discover therapeutic antibodies and bispecific antibodies to treat patients with serious diseases.
Creative Biolabs provides Drosophila neuronal cell line G3-C2 engineered antibodies such as therapeutic antibodies, nanobodies, bispecific antibodies and intrabodies. We also provide antibody / peptide libraries, Biosimilar cell lines, Chimeric antigen receptor (CAR) products, antibody-drug conjugates (ADCs)
Between May 2017 and January 2019, 63 patients have been enrolled. Median age was 54.5 years (range: 24.1-81.7), 53% were female, the median white blood cell count (WBC) was 46.2x109/l (range: 8.61-355.2) and 66.1% carried the p190 fusion. The median follow-up is 8.75 months (range: 0-19.5). So far, 50 patients have completed induction, 43 the 1st cycle of blinatumomab, 36 the 2nd, 24 the 3rd, 20 the 4th and 15 the 5th. Two patients went off protocol for medical decision and toxicity and 1 died during induction. At the end of induction, 13/50 pts (26%) had a molecular response (4 CMR and 9 PNQ). At the primary endpoint (end of 2nd cycle of blinatumomab), 19/35 (54%) had a molecular response (10 CMR and 9 PNQ) and the rate of molecular responses further increased after subsequent cycles (68% and 80% after the 3rd and 4th cycle, respectively). ABL1 mutational analysis, performed in cases with a MRD increase was performed in 11 patients: 6 cases were WT, while mutations were detected in 5 (4 T315I, ...
Title: Selective Chemokine Receptor-Targeted Depletion of Pathological Cells as A Therapeutic Strategy for Inflammatory, Allergic and Autoimmune Diseases. VOLUME: 3 ISSUE: 3. Author(s):John R. McDonald. Affiliation:Osprey Pharmaceuticals Limited, 7150 Frederick, Banting, d, St. Laurent, QC H4S 2A1, Canada.. Keywords:Chemokine, fusion protein, monoclonal antibody, immunotoxin, allergic, autoimmune, inflammation, cancer, bispecific antibodies, ribosome inactivating protein. Abstract: Targeting cell surface antigens or receptors with lytic monoclonal antibodies and specific ligand-directed fusion proteins in order to eliminate cancer cells has been in development for at least forty years. More recently, leukocyte populations known to drive a host of allergic, autoimmune and inflammatory diseases have been targeted. For fusion protein constructs, a number of different classes of cellular toxins have been fused to a variety of ligands such as monoclonal antibodies, growth factors and cytokines. ...
The IsoPlexis system identifies which cells are polyfunctional, i.e. those powerful cells that secrete multiple cytokines and quantitates the cytokine concentrations from each cell. The Polyfunctional Strength Index (PSI) multiplies the number of cytokines secreted per cell with the amount of each cytokine, to identify highly potent immunotherapies.. PSI helps researchers better understand how T cells functionally respond to immunotherapies. It has provided biomarkers and mechanistic insights over the past year to improve the decision-making process for choosing CAR T-cell and bispecific antibody lead candidates.. "The ability to easily perform single-cell proteomics provides a way to understand the complexity of the cellular response to immunotherapy and then to design and test new therapies to enhance efficacy," said Charles Sentman, PhD, Director, Center for Synthetic Immunity, Professor, Geisel School of Medicine, Dartmouth College.. Using the IsoPlexis single-cell proteomics system, ...
CAR T-cell therapies show amazing potential in treating blood cancers, but theres a lot of work to do before the cells are ready for commercialization. Alan Leong, senior analyst with BioWatch, tells The Life Sciences Report about the latest in CAR T-cell therapeutics and how some companies are hedging their bets by developing bispecific antibodies. He also describes the reality behind the growing excitement in regenerative medicine, and what investors should know about some very innovative, but often overlooked, small companies.
Leukemia represents around 3.7% of all new cancer cases and 4.1% of cancer-related deaths in the US, and around 3% of new cancer cases and cancer-associated mortality in the UK. The NIH reports that 60.6% of people survive 5 years or more after a diagnosis of leukemia (based on data from SEER 18 2007-2013). The causes of leukemia are not fully understood, although a variety of genetic, epigenetic and environmental factors are thought to serve a role. Smoking, ionizing radiation, certain chemicals and prior chemotherapy have all been associated with leukemogeneis. Since the early 1990s, the incidence rates of leukemia have gradually increased, for which many reasons could be speculated.. Treatment usually comprises a combination of standard chemotherapy, radiotherapy, targeted therapy and bone marrow transplant. Exciting novel therapies for the treatment of leukemias are being researched, including immunotherapies, such as CAR T-cells and bispecific antibodies, in addition to novel combination ...
EnGeneIC is developing bacterially-derived EDV™ nanocells, loaded with a cytotoxic drug, and externally coated with bispecific antibodies targeting the
Creative Biolabs provides high quality antibody-functionality conjugates generation service to assist your bispecific antibody development.
Harpoon was inspired by Patrick Baeuerle, who led the development work on Micromet BiTE platform, which used an antibody to redirect killer T cells to destroy tumor cells. Amgen went on to acquire Micromet in 2012, back when Roger Perlmutter was running R&D and fell in love with the work. Perlmutter, now running R&D at Merck, brought Baeuerle on board at Amgen to continue work on Blincyto, which was approved in late 2014 as the first bispecific CD19-directed CD3 T-cell engager.. The scientist then left for MPM, bringing along some ideas on how next-wave drugs could go much, much further.. The big idea now, to be tested with HPN424 for prostate cancer, is built around a new platform dubbed TriTAC, for tri-specific T-cell activating drugs. Done properly, the biotech believes it has a better way "to unleash the targeted cell-killing properties of a patients own immune system through T-cell activation." Thats a big goal, and done properly the biotech believes it will penetrate tissue better and ...
NY-ESO-1 is one of the most immunogenic cancer antigens, leading to spontaneous humoral and cellular immune responses in approximately 50% of patients with NY-ESO-1-expressing malignancies (1, 7, 8, 13, 14). Much attention has been paid to monitoring spontaneous and vaccine-induced NY-ESO-1-specific CD8+ T cell responses, which directly mediate the lysis of antigen-expressing tumor cells in vivo (16, 18, 25). However, several studies have indicated that active immunization may be made more efficient by the simultaneous stimulation of antigen-specific CD4+ T cells (21, 26). A number of NY-ESO-1 peptide epitopes presented by different MHC class II molecules have been identified and can be used to explore the role of NY-ESO-1-specific CD4+ T cells in the induction and maintenance of antibody and CD8+ T cell responses against NY-ESO-1 (9, 10, 11, 12).. Spontaneous immunity against NY-ESO-1 was found to be associated with a more favorable clinical outcome in a number of patients analyzed over an ...
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NY-ESO-1 and LAGE-1 are cancer testis antigens with an ideal profile for tumor immunotherapy, combining up-regulation in many cancer types with highly restricted expression in normal tissues and sharing a common HLA-A*0201 epitope, 157-165. Here, we present data to describe the specificity and anti-tumor activity of a bifunctional ImmTAC, comprising a soluble, high-affinity T-cell receptor (TCR) specific for NY-ESO-1157-165 fused to an anti-CD3 scFv. This reagent, ImmTAC-NYE, is shown to kill HLA-A2, antigen-positive tumor cell lines, and freshly isolated HLA-A2- and LAGE-1-positive NSCLC cells. Employing time-domain optical imaging, we demonstrate in vivo targeting of fluorescently labelled high-affinity NYESO-specific TCRs to HLA-A2-, NYESO- 1157-165-positive tumors in xenografted mice. In vivo ImmTAC-NYE efficacy was tested in a tumor model in which human lymphocytes were stably co-engrafted into NSG mice harboring tumor xenografts; efficacy was observed in both tumor prevention and ...
MARTINSRIED, Germany, Sept. 2, 2008 (GLOBE NEWSWIRE) -- MorphoSys AG (Frankfurt:MOR) (Prime Standard Segment, TecDAX) announced today the publication of a first data package for its most advanced proprietary drug development program MOR103, a fully human HuCAL antibody directed against GM-CSF, in the journal "Molecular Immunology". The data presented show that MOR103 is able to block disease-relevant processes such as GM-CSF dependent proliferation and signal transduction in vitro. Additionally, the publication describes that MorphoSys was able to achieve a 5,000-fold increase in affinity and a 2,000-fold increase in potency compared to the parental antibody using its established optimization technology. With a resulting affinity -- or binding strength -- of 400 femtomolar, MOR103 represents the first known anti-GM-CSF agent with a subpicomolar affinity for its target. Targeting of antigens, which are present only at low concentrations in patients such as GM-CSF, will require antibodies with low ...
Meet us at the 4th Antibody Industrial Symposium 2016 (AIS2016) in Montpellier, France.. This meeting organised jointly by LabEx MAbImprove and MabDesign, will be held from July 4th to 5th, 2016 and will bring together scientists, industrials, physicians and policy makers to discuss therapeutic antibodies with a special focus on "Current and Next Generation Antibody Formats".. Dr. Jean-Christophe Rain, Deputy General Manager, will attend this conference. If you have any question about Hybribody he will be happy to answer it and to discuss your project.. Feel free to contact us if you want to arrange a meeting with him during this event.. ...
GSK Biopharm R&D selected Genedata BiologicsTM as their key R&D data management and workflow-support platform. The Genedata Biologics platform supports multiple GSK Biopharm R&D groups spanning lead identification and screening, protein optimization and engineering, and protein production. The system records, manages, and processes data from GSKs diverse antibody discovery platforms such as phage and yeast display, hybridoma, and other technologies, including proprietary ones. In addition, Genedata Biologics helps to improve data quality, increase efficiency through automated upload and export of instrument data, raise experimental throughput, and streamline workflows. Genedata supports the deployment and roll-out of the Genedata Biologics system, its integration into GSKs R&D environment, and its use of GSKs high-throughput automation platforms. Genedata and GSK are working together to support new discovery technologies and next-generation antibody formats such as GSKs domain antibodies and ...
Everything you want to know about the XCD28. Get the inside scoop on the Dell XCD28 from a large number of expert and user reviews.
... - Okay, so many are already green! starting the gallery!Ill modify this post and start putting green people below!These peoples partners can
1MOE: The Crystal Structure of an Anti-CEA scFv Diabody Assembled from T84.66 scFvs in VL-to-VH Orientation: Implications for Diabody Flexibility
This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Monoclonal antibodies, such as blinatumomab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether standard combination chemotherapy is more effective than blinatumomab in treating relapsed B-cell acute lymphoblastic leukemia ...
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 ...
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
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 ...
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 ...
Bi-specific antibody therapeutics potentially allow drug-makers to combine two existing drugs used as a cocktail into one ... Holmes, David (2011). "Buy Buy Bispecific Antibodies". Nature Reviews Drug Discovery. 10: 798. doi:10.1038/nrd3581. PMID ... This is an IgG1-based heterodimeric antibody scaffold that consists of two different heavy chains engineered to exclusively ... DePalma, Angelo (2011). "Improving Classic Antibody Engineering: Diverse Methodologies and Fresh Insights Turn a Good Technique ...
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 ... Baeuerle, Patrick A.; Reinhardt, Carsten (2009-06-15). "Bispecific T-cell engaging antibodies for cancer therapy". Cancer ... 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 ...
... thus obtaining a bispecific antibody (with both Fab and Fcab regions containing distinct binding sites). These bispecific ... 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. ... The other part of an antibody, called the Fab region, contains variable sections that define the specific target that the ...
... (MM-141) is an experimental monoclonal antibody for the treatment of cancer. It is a bispecific antibody targeting ...
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. ...
... a novel factor VIII-mimetic bispecific antibody, in healthy subjects". Blood. 127 (13): 1633-1641. doi:10.1182/blood-2015-06- ... "Factor VIII-Mimetic Function of Humanized Bispecific Antibody in Hemophilia A". New England Journal of Medicine. 374 (21): 2044 ... Emicizumab (trade name Hemlibra) is a humanized monoclonal antibody for the treatment of haemophilia A, developed by Chugai (a ...
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 ...
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 ... NI-0501, an anti-IFNγ antibody, is in development for hemophagocytic lymphohistiocytosis. A phase II/III trial began in 2013 ...
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 ...
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: ... However, CIK cells have the ability to recognize infected or even malignant cells in the absence of antibodies and MHC, ...
... (RG7221) is a bi-specific monoclonal antibody composed of two different heavy chains and two different light chains ... One arm of the antibody binds Angiopoietin-2 (Ang2) and the other is based on bevacizumab (Avastin), binding Vascular ... Vanucizumab (INN) is a humanized monoclonal antibody designed for the treatment of cancer. ... Endothelial Growth Factor A (VEGF-A). The antibody is designed to inhibit both VEGF-A and Ang2 simultaneously to offer superior ...
Blinatumomab, a CD19-CD3 bi-specific monoclonal murine antibody, currently shows promise as a novel pharmacotherapy. By ... 2013). "CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric ... 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 ...
"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 ...
"Targeting of indium 111-labeled bivalent hapten to human melanoma mediated by bispecific monoclonal antibody conjugates: ...
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 ... Solitomab (INN) (MT110) is an artificial bispecific monoclonal antibody that is being investigated as an anti-cancer drug. It ... "Antitumor Activity of an EpCAM/CD3-bispecific BiTE Antibody During Long-term Treatment of Mice in the Absence of T-cell Anergy ... Helwick, Caroline (1 June 2008). "Novel BiTE antibody mediates contact between T cells and cancer cells". Oncology NEWS ...
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 ...
It belongs to a class of constructed monoclonal antibodies, bi-specific T-cell engagers (BiTEs), that exert action selectively ... CD3-bispecific antibody of the BiTE class is far superior to tandem diabody with respect to redirected tumor cell lysis". ... "Business: Antibody advance". Seven Days. Nature (paper). 516 (7530): 149. 11 December 2014. doi:10.1038/516148a. Peter Loftus ( ... Blinatumomab (AMG 103). "Amgen Receives FDA Breakthrough Therapy Designation For Investigational BiTE® Antibody Blinatumomab In ...
Bachelet, I., Munitz, A. and Levi-Schaffer, F. (2006) Abrogation of allergic reactions by a bispecific antibody fragment ... Suppression of normal and malignant Kit signaling by a bispecific antibody linking Kit with CD300a. J. Immunol. 180:6064-6069. ...
Antibodies to GITR have been shown to promote an anti-tumor response through loss of Treg lineage stability. The biotech ... The German biotech company Pieris Pharmaceuticals has developed an engineered lipocalin that is bi-specific for CD137 and HER2 ... Anti-OX40 monoclonal antibodies have been shown to have clinical utility in advanced cancer. The pharma company AstraZeneca has ... "CDX-1127 - Monoclonal Antibody Targeting CD27". Celldex Therapeutics. He LZ, Prostak N, Thomas LJ, Vitale L, Weidlick J, ...
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 ...
The company is focused in developing bispecific monoclonal antibodies using a modular combinatorial approach that engineers the ... Fc fragments with engineered HER2/neu-binding sites and antibody properties". Protein Eng Des. 23 (4): 289-297. doi:10.1093/ ...
Adapter molecules Bi-specific adapter molecules can be administered along with the virus to redirect viral coat protein tropism ... These molecules are fusion proteins that are made up of an antibody raised against the knob domain of the adenovirus coat ...
The bispecific monoclonal antibodies will be directed against CD3 on T-cells and, as the second target, against the ganglioside ... and develop ADCs and bispecific antibodies for two undisclosed targets as well as manufacture a proprietary Celgene antibody ... The deal with EMD Serono is a $300M+ collaboration to discover and develop novel antibody-drug conjugates for several targets ... Sutro entered into a collaboration with Memorial Sloan-Kettering Cancer Center to produce four different bispecific antibodies ...
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 ...
... 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 ...
Bispecific antibodies in the IgG format include asymmetric bispecific antibodies and homodimerized bispecific antibodies, all ... Bispecific antibodies can also be used to treat hemophilia A by mimicking the function of factor VIII. Bispecific antibodies ... new applications were established for bispecific antibodies. Bispecific antibodies that can simultaneously bind to cell surface ... Bispecific antibodies that can inhibit two correlated signaling molecules at the same time can be developed to overcome ...
Bispecific antibodies (bsAbs) participating T cells are rising as a probable. Bispecific antibodies (bsAbs) participating T ... Launch T-cell getting bispecific antibodies (bsAbs) are a appealing device for cancers treatment. This course of antibodies ... Several constructs of bispecific antibodies (bsAbs) to redirect effector T cells ...
Trifunctional antibodies were the first type of bispecific monoclonal antibodies to be produced. The first concepts date back ... antibody as well as pure mouse and pure rat antibody. The trifunctional antibody is extracted chromatographically with protein ... Chames, P; Baty, D (2009). "Bispecific antibodies for cancer therapy: the light at the end of the tunnel". MAbs. 1 (6): 1-9. ... Choi, BD; et, al.; Bigner, DD; Mehta, AI; Kuan, CT; Sampson, JH (2011). "Bispecific antibodies engage T cells for antitumor ...
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 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 ...
Bispecific monoclonal antibody entry in the public domain NCI Dictionary of Cancer Terms Bispecific antibodies at the US ... A bispecific monoclonal antibody (BsMAb, BsAb) is an artificial protein that can simultaneously bind to two different types of ... Bispecific antibodies also have a higher cytotoxic potential, and bind to antigens that are expressed relatively weakly. The ... Chames, P; Baty, D (2009). "Bispecific antibodies for cancer therapy: The light at the end of the tunnel". MAbs. 1 (6): 539-547 ...
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 ...
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. ...
Computationally Designed Bispecific Antibodies using Negative State Repertoires. Title: Computationally Designed Bispecific ... Computationally Designed Bispecific Antibodies using Negative State Repertoires Journal Article - in OSTI.gov 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 ...
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. ...
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 ...
Bispecific antibody targets multiple Pseudomonas aeruginosa evasion mechanisms in the lung vasculature. ... Bispecific antibody targets multiple Pseudomonas aeruginosa evasion mechanisms in the lung vasculature. ... Antibody-mediated inhibition of the T3S protein PcrV did not enhance bacterial phagocytosis but did enhance killing of the few ... A bispecific mAb targeting both Psl and PcrV enhanced neutrophil uptake of P. . aeruginosa. and also greatly increased ...
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 ...
  • The trifunctional antibody is extracted chromatographically with protein A. Using two different species (mouse and rat) has the advantage that less mismatched antibodies are produced because rat light chains preferably pair with rat heavy chains, and mouse light chains with mouse heavy chains. (wikipedia.org)
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