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Polyclonal CTL responses observed in melanoma patients vaccinated with dendritic cells pulsed with a MAGE-3.A1 peptide.

Abstract
Vaccination with mature, monocyte-derived dendritic cells (DC) pulsed with the MAGE-3(168-176) peptide, which is presented by HLA-A1, has been reported to induce tumor regressions and CTL in some advanced stage IV melanoma patients. We present here a precise evaluation of the level of some of these anti-MAGE-3.A1 CTL responses and an analysis of their clonal diversity. Blood lymphocytes were stimulated with the MAGE-3.A1 peptide under limiting dilution conditions and assayed with an A1/MAGE-3 tetramer. This was followed by the cloning of the tetramer-positive cells and by TCR sequence analysis of the CTL clones that lysed targets expressing MAGE-3.A1. We also used direct ex vivo tetramer staining of CD8 cells, sorting, and cloning of the positive cells. In three patients who showed regression of some of their metastases after vaccination, CTL responses were observed with frequencies ranging from 7 x 10(-6) to 9 x 10(-4) of CD8(+) blood T lymphocytes, representing an increase of 20- to 400-fold of the frequencies found before immunization. A fourth patient showed neither tumor regression nor an anti-MAGE-3.A1 CTL response. In each of the responses, several CTL clones were amplified. This polyclonality contrasts with the monoclonality of the CTL responses observed in patients vaccinated with MAGE-3.A1 peptide or with an ALVAC recombinant virus coding for this antigenic peptide.
AuthorsDanièle Godelaine, Javier Carrasco, Sophie Lucas, Vaios Karanikas, Beatrice Schuler-Thurner, Pierre G Coulie, Gerold Schuler, Thierry Boon, Aline Van Pel
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 171 Issue 9 Pg. 4893-7 (Nov 01 2003) ISSN: 0022-1767 [Print] United States
PMID14568970 (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
  • Receptors, Antigen, T-Cell, alpha-beta
  • Vaccines, Subunit
Topics
  • Antigens, Neoplasm (administration & dosage, immunology)
  • CD8-Positive T-Lymphocytes (immunology, metabolism)
  • Cancer Vaccines (administration & dosage, immunology)
  • Clone Cells
  • Cytotoxicity, Immunologic
  • Dendritic Cells (immunology, metabolism, transplantation)
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • HLA-A1 Antigen (immunology)
  • Humans
  • Lung Neoplasms (immunology, prevention & control, secondary)
  • Lymphocyte Culture Test, Mixed
  • Melanoma (immunology, prevention & control, secondary)
  • Neoplasm Proteins (administration & dosage, immunology)
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, alpha-beta (biosynthesis, blood)
  • T-Lymphocytes, Cytotoxic (immunology, metabolism)
  • Vaccines, Subunit (administration & dosage, immunology)

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