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Analysis of a rare melanoma patient with a spontaneous CTL response to a MAGE-A3 peptide presented by HLA-A1.

Abstract
We describe an HLA-A1 melanoma patient who has mounted a spontaneous cytolytic T cell (CTL) response against an antigenic peptide encoded by gene MAGE-A3 and presented by HLA-A1. The frequency of anti-MAGE-3.A1 CTLp was 5 x 10(-7) of the blood CD8 cells, with a dominant clonotype which was present in six out of seven independent anti-MAGE-3.A1 CTL clones. After vaccination with a recombinant poxvirus coding for the MAGE-3.A1 antigen, the blood frequency of anti-MAGE-3.A1 CTLp increased tenfold. Twenty-two independent CTL clones were derived. Surprisingly, only one of them corresponded to the dominant clonotype present before vaccination. Two new clonotypes were repeated 12 and 7 times, respectively. Our interpretation of these results is that the spontaneous anti-MAGE-3.A1 CTL response pre-existing to vaccination was polyclonal, and that the vaccine restimulated only some of these clones. To estimate the incidence of spontaneous anti-MAGE-3.A1 CTL responses in melanoma patients with a tumor expressing gene MAGE-A3, we measured the blood frequency of anti-MAGE-3.A1 T cells in 45 patients, and found only two clear responses.
AuthorsTakeshi Hanagiri, Nicolas van Baren, Bart Neyns, Thierry Boon, Pierre G Coulie
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 55 Issue 2 Pg. 178-84 (Feb 2006) ISSN: 0340-7004 [Print] Germany
PMID16187089 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA-A1 Antigen
  • MAGEA3 protein, human
  • Neoplasm Proteins
Topics
  • Aged
  • Antigens, Neoplasm (administration & dosage, genetics, immunology)
  • Cancer Vaccines (administration & dosage, genetics, immunology)
  • Fatal Outcome
  • Female
  • HLA-A1 Antigen (immunology)
  • Humans
  • Melanoma (drug therapy, immunology)
  • Neoplasm Proteins (administration & dosage, genetics, immunology)
  • T-Lymphocytes, Cytotoxic (immunology)
  • Treatment Failure

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