Syngeneic murine model for prostate cancer using RM1 cells transfected with gp100.

Abstract

Prostate cancer (PC) is the most commonly diagnosed solid tumor in men. A major challenge in PC immunotherapy is the lack of an animal model that resembles human adenocarcinoma and allows for manipulation or monitoring of the immune response. Mouse models are needed for preclinical testing of new immunotherapies, whether used alone or in combination with established drugs, and to develop companion biomarkers that can be validated in clinical trials. To develop a syngeneic prostate adenocarcinoma model with a well-defined tumor antigen, murine RM1 PC cells were transfected with the endogenous mouse melanoma protein, gp100 (RM1-gp100). Gp100 was attractive because it is a self-protein and it instantly allowed us to use the large trove of immune research tools developed for melanoma research. A dendritic cell (DC) vaccine was used as model immunotherapy to demonstrate that adoptive immunotherapy against gp100 decreases the growth of RM1-gp100 but not RM1. Expressing gp100 did not change the growth of RM1 cell in vitro or in vivo. The DCs pulsed with RM1-gp100 could be used to stimulate Pmel-1 lymphocyte proliferation and activation. Pmel-1 lymphocytes could be adoptively transferred into C57Bl/6 mice that were treated with DCs pulsed with RM1-gp100. The resulting Pmel-1 lymphocytes were monitored to assess the primary cellular immune response and memory response. We describe a murine model for prostate adenocarcinoma with a well-characterized antigen that can be used in an immunologically intact mice to monitor the temporal CD8+ lymphocyte-mediated antitumor immunity.