Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells.
There is consensus that an optimized cancer vaccine will have to induce not only CD8+ cytotoxic but also CD4+ T helper (Th) cells, particularly interferon (IFN)-gamma-producing, type 1 Th cells. The induction of strong, ex vivo detectable type 1 Th cell responses has not been reported to date. We demonstrate now that the subcutaneous injection of cryopreserved, mature, antigen-loaded, monocyte-derived dendritic cells (DCs) rapidly induces unequivocal Th1 responses (ex vivo detectable IFN-gamma-producing effectors as well as proliferating precursors) both to the control antigen KLH and to major histocompatibility complex (MHC) class II-restricted tumor peptides (melanoma-antigen [Mage]-3.DP4 and Mage-3.DR13) in the majority of 16 evaluable patients with metastatic melanoma. These Th1 cells recognized not only peptides, but also DCs loaded with Mage-3 protein, and in case of Mage-3DP4-specific Th1 cells IFN-gamma was released even after direct recognition of viable, Mage-3-expressing HLA-DP4+ melanoma cells. The capacity of DCs to rapidly induce Th1 cells should be valuable to evaluate whether Th1 cells are instrumental in targeting human cancer and chronic infections.
Schuler-Thurner
Beatrice
B
Department of Dermatology, University Hospital of Erlangen, D-91052 Erlangen, Germany.
Schultz
Erwin S
ES
Berger
Thomas G
TG
Weinlich
Georg
G
Ebner
Susanne
S
Woerl
Petra
P
Bender
Armin
A
Feuerstein
Bernadette
B
Fritsch
Peter O
PO
Romani
Nikolaus
N
Schuler
Gerold
G
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000276:immunology* / Q000628:therapy; D009363:Neoplasm Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014611:Vaccination
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007376:Interleukin-2; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D015847:Interleukin-4; D007371:Interferon-gamma