Polyclonal CTL responses observed in melanoma patients vaccinated with dendritic cells pulsed with a MAGE-3.A1 peptide.
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.
Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium.
Danièle
D
Godelaine
Javier
J
Carrasco
Sophie
S
Lucas
Vaios
V
Karanikas
Beatrice
B
Schuler-Thurner
Pierre G
PG
Coulie
Gerold
G
Schuler
Thierry
T
Boon
Aline
A
Van Pel
D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015788:HLA-A1 Antigen / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D007959:Lymphocyte Culture Test, Mixed; D008545:Melanoma / Q000276:immunology* / Q000517:prevention & control / Q000556:secondary; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000276:immunology*; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000097:blood; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015788:HLA-A1 Antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D022223:Vaccines, Subunit