Chimeric Mouse-Human IgG1 Antibody that Can Mediate Lysis of Cancer Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 84; no. 10; pp. 3439 - 3443
• Main Authors: Liu, Alvin Y., Robinson, Randy R., Hellstrom, Karl Erik, Murray, E. David, Chang, C. Paul, Hellstrom, Ingegerd
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-05-1987; National Acad Sciences
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antibodies; Antibody dependent cell cytotoxicity; Antibody-Producing Cells - immunology; Antigens; B lymphocytes; Base Sequence; Biological and medical sciences; Cell Line; Cell lines; Chimera; Cloning, Molecular; Colonic Neoplasms - immunology; Complementary DNA; Cytotoxicity, Immunologic; DNA - isolation & purification; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes; Humans; Immunoglobulin G - genetics; Immunoglobulin G - immunology; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Light Chains - genetics; immunoglobulins; Lymphocytes; lymphoid cells; Melanoma - immunology; Mice; Plasmids; Protein Multimerization; Tissue, organ and graft immunology; transfection; Human; Cytolysis; Antibody; Rodentia; Molecular hybrid; IgG1; Vertebrata; Mammalia; Mouse; Immunotherapy; Tumor; Tumor cell; Chimera
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.10.3439

A chimeric mouse-human antibody has been created that recognizes an antigen found on the surface of cells from many carcinomas. Immunoglobulin constant (C) domains of the mouse monoclonal antibody L6, Cγ 2aand Cκ, were substituted by the human Cγ 1and Cκby recombining cDNA modules encoding variable or C domains. The cDNA constructs were transfected into lymphoid cells for antibody production. The chimeric antibody and mouse L6 antibody bound to carcinoma cells with equal affinity and mediated complement-dependent cytolysis. In the presence of human effector cells, the chimeric antibody gave antibody-dependent cellular cytotoxicity at 100 times lower concentration than that needed for the mouse L6 antibody. The chimeric antibody, but not the mouse L6 antibody, is effective against a melanoma line expressing small amounts of the L6 antigen. The findings point to the usefulness of the chimeric antibody approach for obtaining agents with strong antitumor activity for possible therapeutic use in man.