Rapid Induction of Turnor-specific Type 1 T Helper Cells in Metastatic Melanoma Patients by Vaccination with Mature, Cryopreseeved, Peptide-loaded Monocyte-derived Dendritic Cells
Beatrice Schuler-Thurner, Erwin S. Schultz, Thomas G. Berger, Georg Weinlich, Susanne Ebnerf, Petra Woerl, Armin Bender, Bernadette Feuerstein, Peter O. Fritsch, Nikolaus Romani, Gerold Schuler
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)--y-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-y-producing effectors as well as proliferating precursors) both to the control antigen KLH and to major histocompatibility complex (MHC) class II-restricted tumor pep tides (melanoma-antigen [Mage]-3.DP4 and Mage-3.DR13) in the majority of 16 evaluable patients with metastatic melanoma.
These Thl cells recognized not only peptides, but also DCs loaded with Mage-3 protein, and in case of Mage-3DP4-specific Th1 cells IFN-')' was released even after direct recognition of viable, Mage-3-expressing HLA-PP4+ melanoma cells. The capacity of DCs to rapidly induce Thl cells should be valuable to evaluate whether Thl cells are instrumental in targeting human cancer and chronic infections.