Modeling the effect of immunotherapies on human castration-resistant prostate cancer.

In this paper we analyze the potential effect of immunotherapies on castration-resistant form of human Prostate Cancer (PCa). In particular, we examine the potential effect of the dendritic vaccine sipuleucel-T, the only currently available immunotherapy option for advanced PCa, and of ipilimumab, a drug targeting the Cytotoxic T-Lymphocyte Antigen 4 (CTLA4), exposed on the CTLs membrane, currently under Phase II clinical trial. The model, building on the one by Rutter and Kuang, includes different types of immune cells and interactions and is parameterized on available data. Our results show that the vaccine has only a very limited effect on PCa, while repeated treatments with ipilimumab appear potentially capable of controlling and even eradicating an androgen-independent prostate cancer. From a mathematical analysis of a simplified model, it seems likely that, under continuous administration of ipilimumab, the system lies in a bistable situation where both the no-tumor equilibrium and the high-tumor equilibrium are attractive. The schedule of periodic treatments could then determine the outcome, and mathematical models could help determine an optimal schedule.