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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

Beatrice Schuler-Thurner¹, Erwin S. Schultz¹, Thomas G. Berger¹, Georg Weinlich², Susanne Ebner², Petra Woerl¹, Armin Bender¹, Bernadette Feuerstein¹, Peter O. Fritsch², Nikolaus Romani² and Gerold Schuler¹

¹ Department of Dermatology, University Hospital of Erlangen, D-91052 Erlangen, Germany
² Department of Dermatology, University of Innsbruck, A-6020 Innsbruck, Austria

Address correspondence to Gerold Schuler, Dept. of Dermatology, University Hospital of Erlangen, Hartmannstr. 14, D-91052 Erlangen, Germany. Phone: 49-9131-85-1006; Fax: 49-9131-85-6175; E-mail: schuler{at}derma.imed.uni-erlangen.de

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)-–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-–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- 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.

Key Words: dendritic cells • vaccination • CD4⁺ T cells • T helper cells • tumor immunity

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