John Wayne Cancer Institute's (JWCI) polyvalent melanoma cell vaccine (PMCV) consists of three allogeneic melanoma cell lines selected from over fifty of such harvests in 1984. The following criteria melanoma cell lines: 1) they express different MHC Class I antigens, and 2) they contain immunogenic melanoma-associated antigens (MAA) GM2 and GD2. Over the past eleven years, we have utilized these cell lines in several Phase I and II clinical studies of active specific immunotherapy in patients with metastatic melanoma. Vaccine comprised of these lines has proven to be safe and have a therapeutic effect when compared to the natural history control patients treated at JWCI. The past decade has seen the continued discovery of new immunogenic antigens/epitopes expressed by malanoma and the assessment of their therapeutic applicability at molecular, immunological and clinical levels. JWCI's PMCV expresses at least sixteen of MAA known to elicit immune responses in man. Project I will evaluate antibody responses to these specific antigens in order to determine which of the antigen are relevant to disease regression following active specific immunotherapy with PMCV.
The specific aims are: 1) HuMAb will be developed to melanoma-associated recombinant or synthetic protein antigens; 2) epitopes for these antibodies will be determined; 3) binding specificity of antibodies for cancer tissues will be assessed; and 4) anti-tumor activity of antibodies will be tested in vitro and in vivo.
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