Long-term freedom from recurrence in 2 stage IV melanoma patients following vaccination with tyrosinase peptides

Int J Cancer. 2002 May 20;99(3):403-8. doi: 10.1002/ijc.10328.

Abstract

We report here on 2 patients who received adjuvant vaccination with an HLA-A2- or HLA-A24-restricted tyrosinase peptide, respectively, and GM-CSF for frequently relapsing stage IV melanoma. Following resection of metastases and irradiation of brain metastases in 1 patient, both patients were without evidence of disease when receiving the first vaccination. While the patients had had 9 and 12, respectively, mostly s.c., relapses during the 3 years before vaccination, they experienced freedom from relapse for more than 2 years after vaccination. We found a T-cell response to the vaccine peptide in both patients in the peripheral blood by ex vivo IFN-gamma ELISPOT assay. The T-cell population could be further characterized by 4-color flow cytometry in 1 patient, showing that the majority of the peptide-specific CD3(+)CD8(+)IFN-gamma(+) T cells were granzyme B-positive and CCR-7-negative, characterizing them as effector T cells with the ability to mediate cytotoxicity and migrate to inflamed tissues. In this patient also, augmentation of the T-cell response to autologous tumor cells by vaccination could be detected. A single-site postvaccination relapse occurred in both patients, showing downregulation of tyrosinase expression in 1 patient, while normal expression levels for tyrosinase, MHC class I antigens and components of the antigen-processing machinery were found in the other patient. These results suggest that peptide vaccination resulted in a prolonged relapse-free interval in these high-risk patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / prevention & control
  • Brain Neoplasms / secondary
  • CD3 Complex / biosynthesis
  • CD8 Antigens / biosynthesis
  • Cancer Vaccines*
  • Disease-Free Survival
  • Epitopes
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / metabolism
  • Melanoma / diagnosis*
  • Melanoma / pathology
  • Melanoma / prevention & control*
  • Monophenol Monooxygenase / therapeutic use*
  • Neoplasm Metastasis
  • Peptides / chemistry
  • Peptides / therapeutic use
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Recurrence
  • T-Lymphocytes / metabolism
  • Time Factors

Substances

  • CD3 Complex
  • CD8 Antigens
  • Cancer Vaccines
  • Epitopes
  • Peptides
  • RNA, Messenger
  • Interferon-gamma
  • Monophenol Monooxygenase