| Prostate cancer is the most frequently diagnosed noncutaneous cancer among men and a leading cause of cancer deaths. No curative treatment exists for hormone resistant prostate cancer, but immunotherapy has the potential to prevent disease recurrences and to destroy metastases. We investigated the efficacy of immunotherapy in the RM-1 model of prostate cancer. RM-1 cells are aggressive, non-immunogenic mouse prostate cancer cells that express very little MHC I, similar to many human prostate cancers. Our goal was to develop a whole cell tumor vaccine that would generate a protective T cell-dependent antitumor response.; We treated RM-1 tumors in two different ways. In the Pre-infection Vaccine method, RM-1 cells were infected in vitro with recombinant canarypox viruses that produce IL-2, IL-12, and TNF-alpha. The free virus was washed away before the tumors were injected. In the Mix Vaccine method, the viruses and tumor cells were injected together. We hypothesized that introducing the free viruses in vivo would promote T cell involvement in the antitumor immune response. Using either method, 100% of mice rejected the initial challenge, but were not protected upon rechallenge. However, the mice were able to reject more than one challenge with cytokine-secreting RM-1 cells.; Further characterization of the Mix Vaccine-induced immune response revealed that NK cells were necessary and sufficient to reject RM-1 tumors. IFN-gamma and perforin were also required, but Fas Ligand and T cells were not. We concluded that the presence of the viruses in vivo was not sufficient to elicit a T cell response. This was confirmed by the observation that adding free parental virus to the Pre-infection Vaccine did not generate a protective response either. Additional experiments revealed that the Mix Vaccine did not highly activate dendritic cells or T cells in vivo. Although we failed to generate a T cell response, the Mix Vaccine does stimulate a potent NK cell response. NK cell immunotherapy could be effective for low MHC I-expressing tumors for which a T cell response cannot be generated. |
