Evaluation of ricin A chain-containing immunotoxins directed against different epitopes on the delta-chain of cell surface-associated IgD on murine B cells. 1990

R D May, and F D Finkelman, and H T Wheeler, and J W Uhr, and E S Vitetta
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.

Over the past decade, immunotoxins (IT) composed of mAb covalently coupled to toxins or their subunits have been developed for the treatment of malignancies and autoimmune diseases. Despite specific binding to target cells, not every mAb makes a therapeutically potent ricin A chain-containing IT (IT-A). A number of variables influence the potency of a mAb as an IT-A, including the affinity of the mAb, the nature and density of the cell surface Ag, and the type of target cell used. The present report investigates the influence of the epitope specificity of a mAb on the effectiveness of that mAb as an IT-A. Seven mAb directed against different regions of the mouse delta H chain of surface IgD, were conjugated to deglycosylated ricin A chain, and tested for their ability to kill murine B cells. The panel of IT-A had similar A chain activities and similar binding avidities. However, the mAb directed against epitopes in the Fc portion of surface IgD made more effective IT-A than those directed against epitopes in the Fd region. Overall, the anti-Fc-A were approximately 60- to 150-fold more toxic than the anti-Fd-A. Taken together with previous studies, these findings suggest that the epitope on a target Ag recognized by a given mAb is an important variable in determining the potency of a mAb as an IT-A.

UI MeSH Term Description Entries
D007128 Immunoglobulin Fragments Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques. Antibody Fragment,Antibody Fragments,Ig Fragment,Ig Fragments,Immunoglobulin Fragment,Fragment, Antibody,Fragment, Ig,Fragment, Immunoglobulin,Fragments, Antibody,Fragments, Ig,Fragments, Immunoglobulin
D007132 Immunoglobulin Isotypes The classes of immunoglobulins found in any species of animal. In man there are nine classes that migrate in five different groups in electrophoresis; they each consist of two light and two heavy protein chains, and each group has distinguishing structural and functional properties. Antibody Class,Ig Isotype,Ig Isotypes,Immunoglobulin Class,Immunoglobulin Isotype,Antibody Classes,Immunoglobulin Classes,Class, Antibody,Class, Immunoglobulin,Classes, Antibody,Classes, Immunoglobulin,Isotype, Ig,Isotype, Immunoglobulin,Isotypes, Ig,Isotypes, Immunoglobulin
D007138 Immunoglobulin delta-Chains The class of heavy chains found in IMMUNOGLOBULIN D. They have a molecular weight of approximately 64 kDa and they contain about 500 amino acid residues arranged in four domains and an oligosaccharide component covalently bound to the Fc fragment constant region. Ig delta Chains,Immunoglobulins, delta-Chain,Immunoglobulin delta-Chain,delta Immunoglobulin Heavy Chain,delta Immunoglobulin Heavy Chains,delta-Chain Immunoglobulins,Chains, Ig delta,Immunoglobulin delta Chain,Immunoglobulin delta Chains,Immunoglobulins, delta Chain,delta Chain Immunoglobulins,delta Chains, Ig,delta-Chain, Immunoglobulin,delta-Chains, Immunoglobulin
D007141 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. Fc Fragment,Fc Fragments,Fc Immunoglobulin,Fc Immunoglobulins,Ig Fc Fragments,Immunoglobulin Fc Fragment,Immunoglobulins, Fc,Immunoglobulins, Fc Fragment,Fc Fragment Immunoglobulins,Fc Fragment, Immunoglobulin,Fc Fragments, Ig,Fc Fragments, Immunoglobulin,Fragment Immunoglobulins, Fc,Fragment, Fc,Fragments, Ig Fc,Immunoglobulin, Fc
D007143 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. Immunoglobulins, Heavy-Chain,Heavy-Chain Immunoglobulins,Ig Heavy Chains,Immunoglobulin Heavy Chain,Immunoglobulin Heavy Chain Subgroup VH-I,Immunoglobulin Heavy Chain Subgroup VH-III,Heavy Chain Immunoglobulins,Heavy Chain, Immunoglobulin,Heavy Chains, Ig,Heavy Chains, Immunoglobulin,Immunoglobulin Heavy Chain Subgroup VH I,Immunoglobulin Heavy Chain Subgroup VH III,Immunoglobulins, Heavy Chain
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D011947 Receptors, Antigen, B-Cell IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment. Antigen Receptors, B-Cell,B-Cell Antigen Receptor,B-Cell Antigen Receptors,Surface Immunoglobulin,Immunoglobulins, Membrane-Bound,Immunoglobulins, Surface,Membrane Bound Immunoglobulin,Membrane-Bound Immunoglobulins,Receptors, Antigen, B Cell,Surface Immunoglobulins,Antigen Receptor, B-Cell,Antigen Receptors, B Cell,B Cell Antigen Receptor,B Cell Antigen Receptors,Bound Immunoglobulin, Membrane,Immunoglobulin, Membrane Bound,Immunoglobulin, Surface,Immunoglobulins, Membrane Bound,Membrane Bound Immunoglobulins,Receptor, B-Cell Antigen,Receptors, B-Cell Antigen
D003602 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. Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D005434 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. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal

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