IMPROVED SURVIVAL OF PATIENTS WITH MELANOMA WITH AN ANTIBODY-RESPONSETO IMMUNIZATION TO A POLYVALENT MELANOMA VACCINE

Background. Melanoma vaccine treatment appears to slow the progression of melanoma in some patients, particularly in patients in whom it sti mulates cellular antimelanoma immune responses. The relationship of va ccine-induced antibody responses to clinical outcome is less clear. Th e purpose of this study was to investigate the clinical relevance of a ntibody responses to melanoma vaccine immunization. Methods. Eighty-tw o evaluable patients with surgically resected American Joint Committee on Cancer Stage III malignant melanoma were immunized to a partially purified, polyvalent, melanoma antigen vaccine. Antimelanoma antibodie s were measured by immunoprecipitation and sodium dodecyl sulfate-poly acrylamide gel electrophoresis analysis before vaccine treatment and 1 week after the fourth immunization. Results. Vaccine treatment induce d or augmented antibody responses to melanoma in 32 (39%) of the patie nts. The antibodies were directed to one or more antigens of 38-43, 75 , 110, 150 and/or 210 kDs, which previously have been shown to be expr essed preferentially in cultured human melanoma cells. The median dise ase free survival of patients with a vaccine-induced antibody response to one or more of these antigens was 5.4 years compared with 1.4 year s for nonresponders (P = 0.06), and 5-year overall survival was 71% co mpared with 44%, respectively (P = <0.01). As determined by Cox multiv ariate analysis, the difference in overall survival was independent of disease severity or of immunologic competence as evaluated by ability to be sensitized to dinitrochlorobenzene. The difference in survival between antibody responders and nonresponders improved with time. Conc lusions. The antibody response to vaccine treatment is an immune marke r of vaccine activity that appears to be predictive of a later reducti on in the recurrence of melanoma and is unrelated to the vaccine's abi lity to induce cellular immune responses. This finding suggests that v accine treatment may be effective in slowing the progression of melano ma in some patients and that the protective effect is mediated partly by vaccine-induced antimelanoma antibodies.