Treatment options for inoperable, advanced prostate cancer (PrCa) are limited and immunotherapy represents an alternative. The discovery of methods allowing generation of large numbers of dendritic cells (DCs) prompted numerous clinical trials aimed at eliciting tumor specific immunity. However, the optimal strategy for tumor antigen delivery to DCs remains one of the key parameters that need yet to be determined. Killed tumor cells, as a source of tumor associated antigens (TAA), in the DC-based immunization offer a novel strategy that allows presentation of both CTL and T helper epitopes. This may permit presentation of multiple TAA epitopes and a diverse immune response with multiple effectors including CD8 and CD4 T cells, NK cells and macrophages, thus increasing the chances for in vivo tumor rejection. Based on our in vitro results we propose that Dendritic cells loaded with prostate cancer bodies can elicit prostate cancer-specific immune responses in vivo. We propose a clinical trial in 15 HLA-A2.1 patients with hormone-refractory prostate carcinoma who will be vaccinated with autologous monocyte-derived DCs loaded with killed PrCa cell lines (LnCAP and PC3).
Aim 1 : To determine safety and tolerability of DCs loaded with killed allogeneic PrCa cell lines.
Aim 2 : To evaluate the level of immune and clinical responses in patients vaccinated with DCs loaded with killed allogeneic PrCa cell lines. This study will permit us to establish the safety and tolerability of DCs loaded with killed allogeneic tumor cells as a source of TAA. It will also permit us to gain insights into the level of prostate cancer immunity induced by DCs.
