Type-I Polarized Dendritic Cells Loaded with Apoptotic Prostate Cancer Cells Are Potent Inducers of CD8+ T cells against Prostate Cancer Cells and Defined Prostate Cancer-Specific Epitopes

BACKGROUND. In order to develop improved vaccines for patients with recurrent prostate cancer (PCa), we tested the feasibility of using type-1 polarized dendritic cells (alpha DC1s) to cross-present antigens from allogeneic PCa cells and to induce functional CD8(+) T cell responses against PCa cells and against defined MHC class I-restricted PCa-relevant epitopes. METHODS. Monocyte-derived DCs from PCa patients were matured using the "standard" cytokine cocktail (IL-1 beta/TNF alpha/IL-6/PGE(2)) or using the alpha DC1-polarizing cocktail (IL-1 beta/TNF alpha/IFN alpha/IFN gamma/poly-I:C), loaded with UV-irradiated LNCaP cells, and used to sensitize autologous CD8(+) T cells. RESULTS. alpha DC1s from PCa patients secreted 10-30 times higher levels of IL-12p70 than sDCs. Importantly this elevated capacity for IL-12p70 secretion was not inhibited by loading with apoptotic tumor cells. Compared to standard DCs, alpha DC1s induced higher numbers of CD8(+) T cells capable of recognizing both the original PCa cells as well as another PCa cell line, DU145, in MHC class I-restricted fashion. Furthermore, aDC1s induced higher numbers of CD8(+) T cells recognizing defined PCa-specific class I-restricted peptide epitopes of prostate-specific antigen and prostatic acid phosphatase: PAP(135-143) (average 49-fold higher), PAP(112-120) (average 24-fold), PSA(141-150) (average 5.5-fold), and PSA(146-154) (average 11-fold). CONCLUSION. Type-1 polarization of GM-CSF/IL-4-generated DCs enhances their ability to present allogeneic tumor cells and to induce CD8(+) T cells recognizing different PCa cells and multiple defined PCa-specific epitopes. These observations help to develop improved immunotherapies of PCa for patients with different HLA types and lacking autologous tumor material. Prostate 71: 125-133, 2011. (C) 2010 Wiley-Liss, Inc.