MURINE MONOCLONAL ANTI-IDIOTOPE ANTIBODY BREAKS UNRESPONSIVENESS AND INDUCES A SPECIFIC ANTIBODY-RESPONSE TO HUMAN MELANOMA-ASSOCIATED PROTEOGLYCAN ANTIGEN IN CYNOMOLGUS MONKEYS

The mouse monoclonal antibody MEM136 (mAb1) is directed against an epi tope on human melanoma-associated proteoglycan antigen (MPG). This epi tope is also present on various normal human and subhuman tissues. A m onoclonal murine anti-idiotope (anti-Id) antibody (mAb2), designated I -Mel-2, was generated against MEM136 and used as a surrogate antigen f or the MPG molecule. I-Mel-2 was tested in cynomolgus monkeys (Macaca fascicularis) for its ability to induce anti-MPG humoral responses. Al l monkeys immunized with Ab2 developed specific anti-anti-idiotype (Ab 3) responses that were capable of inhibiting binding of Ab2 to Ab1. Fu rthermore, I-Mel-2 immune monkey serum contained anti-MPG antibodies ( Ab1') that bound to MPG-positive but not to MPG-negative melanoma cell lines. Monkeys immunized with Colo38 melanoma cells (membrane-bound M PG antigen) did not contain anti-MPG antibodies that inhibited the bin ding of two distinct anti-MPG mAb I-125-labeled MEM136 or I-125-labele d 225.28 to Colo38 cells. The induction of anti-MPG responses in monke ys did not cause any apparent side effects in animals, despite the fac t that the MPG antigen is expressed by many normal tissues. The affini ty-purified, I-Mel-2 idiotype-specific, Ab3 immunoprecipitated MPG ant igen from melanoma cells. Furthermore, the I-Mel-2-induced Ab3 inhibit ed melanoma cell invasion in an in vitro assay, implying that these an tibodies have biological significance.