Transient expansion of peptide-specific lymphocytes producing IFN-gamma after vaccination with dendritic cells pulsed with MAGE peptides in patients with mage-A1/A3-positive tumors.
Assessment of T-cell activation is pivotal for evaluation of cancer immunotherapy. We initiated a clinical trial in patients with MAGE-A1 and/or -A3 tumors using autologous DC pulsed with MAGE peptides aimed at analyzing T-cell-derived, IFN-gamma secretion by cytokine flow cytometry and ELISPOT. We also tested whether further KLH addition could influence this response favorably. Monocyte-derived DC were generated from leukapheresis products. They were pulsed with the relevant MAGE peptide(s) alone in group A (n=10 pts) and additionally with KLH in group B (n=16 pts). A specific but transient increase in the number of peripheral blood T lymphocytes secreting IFN-gamma in response to the vaccine peptide(s) was observed in 6/8 patients of group A and in 6/16 patients of group B. We conclude that anti-tumor vaccination using DC pulsed with MAGE peptides induces a potent but transient anti-MAGE, IFN-gamma secretion that is not influenced by the additional delivery of a nonspecific, T-cell help.
Toungouz
M
M
Unité de Thérapie Cellulaire et Moléculaire (U.T.C.M.), Erasme Hospital and Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium. toungouz@ulb.ac.be
Libin
M
M
Bulté
F
F
Faid
L
L
Lehmann
F
F
Duriau
D
D
Laporte
M
M
Gangji
D
D
Bruyns
C
C
Lambermont
M
M
Goldman
M
M
Velu
T
T
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D018450:Disease Progression; D005260:Female; D006433:Hemocyanins / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D016896:Treatment Outcome; D014611:Vaccination
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; C420909:Mage-a2 antigen; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin