title: Immunization of HLA-A*0201 and/or HLA-DPbeta1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen.
abstract: HLA class I-restricted peptides are often used in peptide vaccine regimens. There is strong evidence that many of these peptides can generate specific CD8 T-cell responses in vivo; however, only occasional objective clinical responses have been reported. To test whether provision of "help" would enhance antitumor immunity, the authors initiated a clinical trial in which patients with metastatic melanoma were immunized against the NY-ESO-1 tumor antigen, using an HLA-A2-restricted peptide (ESO-1:165V), an HLA-DP4-restricted peptide (NY-ESO-1:161-180), or both peptides given concomitantly. The first cohorts received only ESO-1:165V, using three vaccination schedules. Immunologically, most patients developed immune responses to the HLA-A2-restricted native ESO-1 epitope after vaccination. Peptide vaccine given daily for 4 days appeared to induce immunologic responses more rapidly than if given once a week or once every 3 weeks. In contrast, vaccination using the NY-ESO-1:161-180 peptide induced immune responses in only a few patients. Clinically, one patient who received NY-ESO-1:161-180 peptide alone had a partial response lasing 12 months. Concomitant vaccination with the HLA class II-restricted peptide did not alter the immune response to the HLA class I-restricted peptide form NY-ESO-1. However, vaccination with the HLA-A2-restricted epitope generated primarily T cells that did not recognize tumor after in vitro sensitization. This result raises questions about the use of synthetic peptides derived from NY-ESO-1 as a sole form of immunization.
authors.affiliation: Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1502, USA.
authors.forename: Hung T
authors.initials: HT
authors.lastname: Khong
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Topalian
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Mavroukakis
authors.forename: Donald E
authors.initials: DE
authors.lastname: White
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology* / Q000627:therapeutic use / Q000633:toxicity; D015789:HLA-A2 Antigen; D006682:HLA-DP Antigens / Q000276:immunology* / Q000627:therapeutic use / Q000633:toxicity; D059868:HLA-DP beta-Chains; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; C499603:ESO-1:165V peptide, human; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C056284:HLA-DPw4 antigen; D016056:Immunodominant Epitopes; D007376:Interleukin-2; D008565:Membrane Proteins; C499604:NY-ESO-1:161-180 peptide, human; D007371:Interferon-gamma