Generation of potent cytotoxic T lymphocytes against castration resistant prostate cancer cells by dendritic cells loaded with dying allogeneic prostate cancer cells - Abstract

To induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)-based immunotherapy against prostate cancer, various tumor antigens should be loaded onto DCs.

The aim of this study was to establish a method of immunotherapy for castration resistant prostate cancer (CRPC) using prostate cancer-specific CTLs generated in vitro by DCs. Monocyte-derived DCs from CRPC patients were induced to mature using a standard cytokine cocktail (in IL-1β, TNF-α, IL-6, and PGE2 : standard DCs, sDCs) or using an α-type 1-polarized DC (αDC1) cocktail (in IL-1β, TNF-α, IFN-α, IFN-γ, and polyinosinic:polycytidylic acid) and loaded with the UVB-irradiated CRPC cell line PC-3. Antigen-loaded DCs were evaluated by morphological and functional assays. The αDC1s significantly increased the expression of several molecules related to DC maturation, regardless of whether the αDC1s were loaded with tumor antigens or not, compared to sDCs. The αDC1s showed a higher production of interleukin-12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumor antigens, as compared to standard DCs (sDCs). Prostate cancer-specific CTLs against autologous CRPC cells were successfully induced by αDC1s loaded with dying PC-3 cells. Autologous αDC1s loaded with an allogeneic CRPC cell line can generate greater CRPC-specific CTL responses as compared to sDCs and may provide a novel source of DC-based vaccines that can be used for the development of immunotherapy in patients with CRPC.

Written by:
Hwang EC, Lim MS, Im CM, Kwon DD, Lee HJ, Nguyen-Pham TN, Lee YK, Lee JJ.   Are you the author?
Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeollanamdo, Republic of Korea; Departments of Urology, Chonnam National University Hwasun Hospital.

Reference: Scand J Immunol. 2012 Nov 6. Epub ahead of print.
doi: 10.1111/sji.12007

PubMed Abstract
PMID: 23126536