Monoclonal anti-MAGE-3 CTL responses in melanoma patients displaying tumor regression after vaccination with a recombinant canarypox virus.
We have analyzed the T cell responses of HLA-A1 metastatic melanoma patients with detectable disease, following vaccination with a recombinant ALVAC virus, which bears short MAGE-1 and MAGE-3 sequences coding for antigenic peptides presented by HLA-A1. To evaluate the anti-MAGE CTL responses, we resorted to antigenic stimulation of blood lymphocytes under limiting dilution conditions, followed by tetramer analysis and cloning of the tetramer-positive cells. The clones were tested for their specific lytic ability and their TCR sequences were obtained. Four patients who showed tumor regression were analyzed, and an anti-MAGE-3.A1 CTL response was observed in three of these patients. Postvaccination frequencies of anti-MAGE-3.A1 CTL were 3 x 10(-6), 3 x 10(-3), and 3 x 10(-7) of the blood CD8 T cells, respectively. These three responses were monoclonal. No anti-MAGE-1.A1 CTL response was observed. These results indicate that, like peptide immunization, ALVAC immunization produces monoclonal responses. They also suggest that low-level antivaccine CTL responses can initiate a tumor regression process. Taken together, our analysis of anti-MAGE-3.A1 T cell responses following peptide or ALVAC vaccination shows a degree of correlation between CTL response and tumor regression, but firm conclusions will require larger numbers.
Cellular Genetics Unit, Institute of Cellular Pathology, Université de Louvain, Brussels, Belgium.
Vaios
V
Karanikas
Christophe
C
Lurquin
Didier
D
Colau
Nicolas
N
van Baren
Charles
C
De Smet
Bernard
B
Lethé
Thierry
T
Connerotte
Véronique
V
Corbière
Marie-Ange
MA
Demoitié
Danielle
D
Liénard
Brigitte
B
Dréno
Thierry
T
Velu
Thierry
T
Boon
Pierre G
PG
Coulie
D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D028121:Canarypox virus / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D008207:Lymphatic Metastasis / Q000276:immunology / Q000517:prevention & control; D008545:Melanoma / Q000276:immunology* / Q000517:prevention & control* / Q000556:secondary; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000097:blood; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
C078788:ALVAC vaccine; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D014765:Viral Vaccines