Anti-Tac-H, a humanized antibody to the interleukin 2 receptor with new features for immunotherapy in malignant and immune disorders. 1990

R P Junghans, and T A Waldmann, and N F Landolfi, and N M Avdalovic, and W P Schneider, and C Queen
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

The Mr 55,000 interleukin 2 receptor peptide (Tac; CD25) is not expressed by normal resting T-cells but is markedly up-regulated in adult T-cell leukemia and other malignancies, as well as on T-cells activated in normal immune, autoimmune, allograft, and graft-versus-host settings. Anti-Tac is a mouse monoclonal antibody directed against the Tac peptide. Our prior attempts to use this antibody in humans for antitumor therapy and immune regulation have been limited by weak recruitment of effector functions and neutralization by antibodies to mouse immunoglobulins. To circumvent these difficulties, we prepared several chimeric "humanized" anti-Tac antibodies by genetic engineering, including one "hyperchimeric" antibody (anti-Tac-II) in which the molecule is human except for the small hypervariable segments of the complementarity-determining regions retained from the mouse antibody. These constructs maintain high affinities for antigen and abilities to block T-cell activation and demonstrate new capabilities to perform antibody-dependent cell-mediated cytotoxicity, absent in the mouse anti-Tac. Hence, humanized antibodies have been developed to a tumor-associated antigen and activated T-cell marker with significant features that offer new therapeutic possibilities for select neoplastic and immune disorders.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007158 Immunologic Techniques Techniques used to demonstrate or measure an immune response, and to identify or measure antigens using antibodies. Antibody Dissociation,Immunologic Technic,Immunologic Technics,Immunologic Technique,Immunological Technics,Immunological Techniques,Technic, Immunologic,Technics, Immunologic,Technique, Immunologic,Techniques, Immunologic,Antibody Dissociations,Dissociation, Antibody,Dissociations, Antibody,Immunological Technic,Immunological Technique,Technic, Immunological,Technics, Immunological,Technique, Immunological,Techniques, Immunological
D002678 Chimera An individual that contains cell populations derived from different zygotes. Hybrids,Chimeras,Hybrid
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000888 Antibodies, Anti-Idiotypic Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies. Anti-Antibodies,Anti-Idiotype Antibodies,Antibodies, Internal Image,Antigamma Globulin Antibodies,Antiglobulins,Anti Antibodies,Anti-gamma Globulin Antibodies,Anti Idiotype Antibodies,Anti gamma Globulin Antibodies,Anti-Idiotypic Antibodies,Antibodies, Anti,Antibodies, Anti Idiotypic,Antibodies, Anti-Idiotype,Antibodies, Anti-gamma Globulin,Antibodies, Antigamma Globulin,Globulin Antibodies, Anti-gamma,Globulin Antibodies, Antigamma,Image Antibodies, Internal,Internal Image Antibodies
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D000920 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. ADCC,Cytotoxicity, Antibody-Dependent Cell,Cell Cytoxicity, Antibody-Dependent,Antibody Dependent Cell Cytotoxicity,Antibody-Dependent Cell Cytotoxicities,Antibody-Dependent Cell Cytoxicities,Antibody-Dependent Cell Cytoxicity,Cell Cytotoxicities, Antibody-Dependent,Cell Cytotoxicity, Antibody-Dependent,Cell Cytoxicities, Antibody-Dependent,Cell Cytoxicity, Antibody Dependent,Cytotoxicities, Antibody-Dependent Cell,Cytotoxicity, Antibody Dependent Cell,Cytoxicities, Antibody-Dependent Cell,Cytoxicity, Antibody-Dependent Cell
D015375 Receptors, Interleukin-2 Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN. IL-2 Receptors,Interleukin-2 Receptor,Interleukin-2 Receptors,Receptors, IL-2,Receptors, T-Cell Growth Factor,T-Cell Growth Factor Receptors,IL-2 Receptor,IL2 Receptor,IL2 Receptors,Interleukin 2 Receptor,Receptor, TCGF,T-Cell Growth Factor Receptor,TCGF Receptor,TCGF Receptors,IL 2 Receptor,IL 2 Receptors,Interleukin 2 Receptors,Receptor, IL-2,Receptor, IL2,Receptor, Interleukin 2,Receptor, Interleukin-2,Receptors, IL 2,Receptors, IL2,Receptors, Interleukin 2,Receptors, T Cell Growth Factor,Receptors, TCGF,T Cell Growth Factor Receptor,T Cell Growth Factor Receptors
D015459 Leukemia-Lymphoma, Adult T-Cell Aggressive T-Cell malignancy with adult onset, caused by HUMAN T-LYMPHOTROPIC VIRUS 1. It is endemic in Japan, the Caribbean basin, Southeastern United States, Hawaii, and parts of Central and South America and sub-Saharan Africa. ATLL,HTLV I Associated T Cell Leukemia Lymphoma,HTLV-Associated Leukemia-Lymphoma,HTLV-I-Associated T-Cell Leukemia-Lymphoma,Human T Lymphotropic Virus Associated Leukemia Lymphoma,Human T Lymphotropic Virus-Associated Leukemia-Lymphoma,Human T-Cell Leukemia-Lymphoma,Leukemia Lymphoma, Adult T Cell,Leukemia Lymphoma, T Cell, Acute, HTLV I Associated,Leukemia, Adult T-Cell,Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated,T Cell Leukemia Lymphoma, HTLV I Associated,T Cell Leukemia, Adult,T-Cell Leukemia, Adult,T-Cell Leukemia-Lymphoma, Adult,T-Cell Leukemia-Lymphoma, HTLV-I-Associated,Adult T-Cell Leukemia,Adult T-Cell Leukemia-Lymphoma,Adult T-Cell Leukemia-Lymphomas,Adult T-Cell Leukemias,HTLV Associated Leukemia Lymphoma,HTLV-Associated Leukemia-Lymphomas,HTLV-I-Associated T-Cell Leukemia-Lymphomas,Human T Cell Leukemia Lymphoma,Human T-Cell Leukemia-Lymphomas,Leukemia, Adult T Cell,Leukemia-Lymphoma, HTLV-Associated,Leukemia-Lymphoma, HTLV-I-Associated T-Cell,Leukemia-Lymphoma, Human T-Cell,Leukemia-Lymphomas, Adult T-Cell,Leukemia-Lymphomas, HTLV-Associated,Leukemia-Lymphomas, HTLV-I-Associated T-Cell,Leukemia-Lymphomas, Human T-Cell,Leukemias, Adult T-Cell,T Cell Leukemia Lymphoma, Adult,T-Cell Leukemia-Lymphoma, Human,T-Cell Leukemia-Lymphomas, Adult,T-Cell Leukemia-Lymphomas, HTLV-I-Associated,T-Cell Leukemia-Lymphomas, Human,T-Cell Leukemias, Adult

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