Identification of HLA-A*03, A*11 and B*07-restricted melanoma-associated peptides that are immunogenic in vivo by vaccine-induced immune response (VIIR) analysis

With the discovery of increasing numbers of tumor antigens, there is a need to rapidly determine whether these antigens and the individual peptides th ey express are able to stimulate immune responses in vivo and thus, can be used to construct cancer vaccines. In this study we used the method of vacc ine-induced immune response (VIIR) analysis to identify multiple immunogeni c peptide epitopes derived from several melanoma associated antigens and pr esented by HLA-A*03, A*11 and B*07. Thirty-one patients with melanoma were immunized to a polyvalent vaccine containing multiple antigens, including M AGE-3, Melan A/MART-1, gp100 and tyrosinase. Their peripheral blood was tes ted for peptide-specific, vaccine-induced CD8+ T cell responses before and after immunization using an enzyme-linked immune spot (ELISPOT) assay with panels of peptides restricted by these three alleles. The peptides were sel ected for immunogenic potential based on their strong binding affinity in v itro to HLA-A*03, A*11 or B*07. Overall, 60% of the 20 peptides studied wer e recognized by at least one patient and 50% of the patients showed a vacci ne-induced CD8+ T cell response to at least one peptide that matched their HLA specificity. We conclude that VIIR analysis is an effective strategy to directly identify immunogenic peptides that are good candidates for vaccin e construction. (C) 2000 Elsevier Science B.V. All rights reserved.