Vaccination of a melanoma patient with mature dendritic cells pulsed with MAGE-3 peptides triggers the activity of nonvaccine anti-tumor cells.
We previously characterized the CTL response of a melanoma patient who experienced tumor regression following vaccination with an ALVAC virus coding for a MAGE-A3 Ag. Whereas anti-vaccine CTL were rare in the blood and inside metastases of this patient, anti-tumor CTL recognizing other tumor Ags, mainly MAGE-C2, were 100 times more frequent in the blood and considerably enriched in metastases following vaccination. In this study we report the analysis of the CTL response of a second melanoma patient who showed a mixed tumor response after vaccination with dendritic cells pulsed with two MAGE-A3 antigenic peptides presented, respectively, by HLA-A1 and HLA-DP4. Anti-MAGE-3.A1 CD8 and anti-MAGE-3.DP4 CD4 T cells became detectable in the blood after vaccination at a frequency of approximately 10(-5) among the CD8 or CD4 T cells, respectively, and they were slightly enriched in slowly progressing metastases. Additional anti-tumor CTL were present in the blood at a frequency of 2x10(-4) among the CD8 T cells and, among these, an anti-MAGE-C2 CTL clone was detected only following vaccination and was enriched by >1,000-fold in metastases relative to the blood. The striking similarity of these results with our previous observations further supports the hypothesis that the induction of a few anti-vaccine T cells may prime or restimulate additional anti-tumor T cell clones that are mainly responsible for the tumor regression.
Carrasco
Javier
J
Ludwig Institute for Cancer Research, Cellular Genetics Unit, Université Catholique de Louvain, Brussels, Belgium.
Van Pel
Aline
A
Neyns
Bart
B
Lethé
Bernard
B
Brasseur
Francis
F
Renkvist
Nicolina
N
van der Bruggen
Pierre
P
van Baren
Nicolas
N
Paulus
Robert
R
Thielemans
Kris
K
Boon
Thierry
T
Godelaine
Danièle
D
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000276:immunology; D002461:Cell Line, Transformed; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D020014:K562 Cells; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000473:pathology / Q000556:secondary / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments