Immunization of HLA-A*0201 and/or HLA-DPβ1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen

Hung T. Khong, James C. Yang, Suzanne L. Topalian, Richard M. Sherry, Sharon A. Mavroukakis, Donald E. White, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)472-477
Number of pages6
JournalJournal of Immunotherapy
Volume27
Issue number6
DOIs
StatePublished - 2004

Keywords

  • Cancer vaccine
  • HLA-A2
  • HLA-DP
  • NY-ESO-1
  • Tumor antigens

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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