title: 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.
abstract: With the discovery of increasing numbers of tumor antigens, there is a need to rapidly determine whether these antigens and the individual peptides they 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 vaccine-induced immune response (VIIR) analysis to identify multiple immunogenic peptide epitopes derived from several melanoma associated antigens and presented by HLA-A*03, A*11 and B*07. Thirty-one patients with melanoma were immunized to a polyvalent vaccine containing multiple antigens, including MAGE-3, Melan A/MART-1, gp100 and tyrosinase. Their peripheral blood was tested 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 selected for immunogenic potential based on their strong binding affinity in vitro to HLA-A*03, A*11 or B*07. Overall, 60% of the 20 peptides studied were recognized by at least one patient and 50% of the patients showed a vaccine-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 vaccine construction.
authors.affiliation: The Ronald O. Perelman Department of Dermatology, New York University Medical Center, New York, NY 10016, USA. srr3@is.nyu.edu
authors.forename: S R
authors.initials: SR
authors.lastname: Reynolds
authors.forename: E
authors.initials: E
authors.lastname: Celis
authors.forename: A
authors.initials: A
authors.lastname: Sette
authors.forename: R
authors.initials: R
authors.lastname: Oratz
authors.forename: R L
authors.initials: RL
authors.lastname: Shapiro
authors.forename: D
authors.initials: D
authors.lastname: Johnston
authors.forename: M
authors.initials: M
authors.lastname: Fotino
authors.forename: J C
authors.initials: JC
authors.lastname: Bystryn
mesh_terms: D000483:Alleles; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D059870:HLA-A11 Antigen; D015791:HLA-A3 Antigen / Q000235:genetics / Q000276:immunology; D015793:HLA-B7 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000276:immunology; D014442:Monophenol Monooxygenase / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D017778:Vaccines, Combined; D058951:gp100 Melanoma Antigen
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D015791:HLA-A3 Antigen; D015793:HLA-B7 Antigen; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D017778:Vaccines, Combined; D058951:gp100 Melanoma Antigen; C094534:polyvalent melanoma cell vaccine; D014442:Monophenol Monooxygenase