title: 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.
authors.affiliation: Christian de Duve Institute of Cellular Pathology, University of Louvain, Avenue Hippocrate 74, UCL 7459, 1200 Brussels, Belgium.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hanagiri
authors.forename: Nicolas
authors.initials: N
authors.lastname: van Baren
authors.forename: Bart
authors.initials: B
authors.lastname: Neyns
authors.forename: Thierry
authors.initials: T
authors.lastname: Boon
authors.forename: Pierre G
authors.initials: PG
authors.lastname: Coulie
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D017809:Fatal Outcome; D005260:Female; D015788:HLA-A1 Antigen / Q000276:immunology*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology*; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D017211:Treatment Failure
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015788:HLA-A1 Antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins