Stimulation of CD8+ T Cell Responses to MAGE-3 and Melan A/MART-1 by Immunization to a Polyvalent Melanoma Vaccine

Int J Cancer. 1997 Sep 17;72(6):972-6. doi: 10.1002/(sici)1097-0215(19970917)72:6<972::aid-ijc9>3.0.co;2-m.

Abstract

A critical requirement for cancer vaccines is that they stimulate CD8+ T cell responses. In this study, we tested the ability of a polyvalent melanoma vaccine to induce CD8+ T cell responses to the melanoma associated antigens MAGE-3 and Melan A/MART-1. Fifteen HLA-A2+ patients with resected malignant melanoma were immunized with the vaccine s.c. every 2-3 weeks. CD8+ T cells in peripheral blood reacting to HLA-A2 restricted epitopes on MAGE-3 (FLWGPRALV) and Melan A/MART-1/(AAGIGILTV) were quantitated using a filter spot assay at baseline and following 4 immunizations. Vaccine immunization induced CD8+ T cells reacting to one or both of these peptides in 9 of the 15 (60%) patients. These cells were CD8+ and HLA-A2 restricted, as reactivity was abrogated by monoclonal antibodies (MAbs) to CD8 and class I HLA, but not by anti-CD4. All responding patients remained recurrence-free for at least 12 months (median 15 months, range 12 to >21 months), whereas melanoma recurred within 3-5 months in non-responders. The differences in outcome were unrelated to differences in disease severity or overall immunological competence between responders and non-responders. Our results demonstrate directly that MAGE-3 and Melan A/MART-1 can stimulate CD8+ T cell responses in humans, and suggest that these responses are protective and surrogate markers of vaccine efficacy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines*
  • Disease-Free Survival
  • Epitopes / immunology
  • HLA-A2 Antigen / immunology
  • Humans
  • MART-1 Antigen
  • Melanoma / immunology*
  • Melanoma / pathology
  • Melanoma / therapy*
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / immunology*
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes
  • HLA-A2 Antigen
  • MAGEA3 protein, human
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins