Immunotherapy of murine sarcomas with auto-anti-idiotypic monoclonal antibodies which bind to tumor-specific T cells.
Hybridomas producing monoclonal antibodies (mAb) were obtained from BALB/c mice immunized against either of two transplanted, chemically induced syngeneic sarcomas, MCA-1490 or MCA-1511. Two mAb, 4.72 and 5.96, were obtained, one from each immunization. They were found to have apparent anti-idiotypic specificity in that they, when injected s.c., primed naive BALB/c mice for delayed-type hypersensitivity that was specific for the immunizing tumor and required homology at genes linked to the Igh-1 allotype locus. Neither mAb bound tumor antigen. When mice with established transplants of MCA-1490 or MCA-1511 were treated by repeated i.p. injections of the appropriate anti-idiotypic mAb (4.72 and 5.96, respectively), a significant reduction in tumor growth was observed in those mice that had received the appropriate mAb. The idiotope defined by mAb 4.72 was expressed by T cells in mice responding to MCA-1490. mAb 4.72 bound to T cell suppressor factors that were specific for MCA-1490 and were derived from T cell hybridomas or sera of mice bearing MCA-1490. mAb 4.72 also bound to cells from lymph nodes draining the area of a growing MCA-1490 tumor. It was used, in combination with cell sorting, to establish a T cell line, which mediated delayed-type hypersensitivity to MCA-1490 and inhibited the outgrowth of MCA-1490 in BALB/c mice. Thus, mAb specific for idiotopes on T cells responding to syngeneic tumor antigen had both direct immunotherapeutic activity and could be used to establish cultures of tumor-reactive T cells.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007167:Immunotherapy; D051379:Mice; D012513:Sarcoma, Experimental / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes