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

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.

• Authors: Carmen Scheibenbogen, Dirk Nagorsen, Barbara Seliger, Alexander Schmittel, Anne Letsch, Sandra Bauer, Nicole Max, Michaela Bock, Derek Atkins, Eckhard Thiel, Ulrich Keilholz
• Journal: International journal of cancer (Int J Cancer) Vol. 99 Issue 3 Pg. 403-8 (May 20 2002) ISSN: 0020-7136 [Print] United States
• PMID: 11992409 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

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

Topics

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