Identification of immunogenic human melanoma antigens in a polyvalent melanoma vaccine.

An essential element in the development of effective vaccines against human malignant melanoma is the identification of antigens which are relevant for vaccine construction as evidenced by their ability to stimulate antimelanoma immune responses in humans. In this study, we identified immunogenic melanoma antigens using as probes antibodies induced in patients immunized with a vaccine which contains a broad range of potential immunogens. By immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of detergent lysates of radioiodinated melanoma cells, we found that 17 (65%) of 26 patients sequentially immunized with a polyvalent melanoma antigen vaccine developed antibodies to one or more melanoma cell surface antigens with approximate molecular weights of 38,000-43,000, 75,000, 110,000, 150,000, and 210,000. The immunodominant antigens which most frequently stimulated antibody responses were the M(r) 110,000 antigen followed by the M(r) 210,000 and 38,000-43,000 antigens, which induced antibody responses in 62%, 27%, and 19% of patients, respectively. These three antigens were commonly expressed on different melanomas but rarely on nonmelanoma cells and are unrelated to class I or II human leukocyte antigens or to the previously described p97 or M(r) 240,000 proteoglycan melanoma-associated antigens. Thus, these three antigens are attractive candidates for the construction of melanoma vaccines, because they are immunogenic in humans and are preferentially expressed on melanomas.