Both the incidence and mortality of malignant melanoma are rising at a rate now estimated to double every 10-15 years. Treatment of the advanced stages of the disease remains unsatisfactory, and new strategies are being sought. The development of monoclonal antibody technology and, more importantly, the recent demonstration of clinical response to the administration of monoclonal antibody in patients with advanced melanoma have stimulated renewed interest in the immunotherapy of this disease. This proposal is addressed at the further definition of the role of monoclonal antibodies in the diagnosis and treatment of malignant melanoma. All phases of the development of the antibodies are included, from the production and specificity testing, to in vitro evaluation of the specific biologic properties of the antibodies, including binding characteristics, direct cytostatic/cytotoxic effects, antibody mediated complement dependent cytotoxicity, and antibody dependent cellular cytotoxicity (ADCC). Further in vivo studies on localization and therapy in animal models will be performed after purification and safety testing. Promising antibodies will be introduced into clinical trials of localization and therapy. Therapeutic proposals include the administration of single antibodies, combinations of antibodies, concurrent antibody and various chemotherapeutic agents, and investigation of alternate routes of administration (eg intralymphatic, intra arterial isolation perfusion). Modifications of antibodies that do not mediate significant biologic effector functions are being investigated in other areas of the laboratory, and will be evaluated as the technology becomes available (eg antibody conjugates, class switching).
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