Combining Treg Depletion with Androgen Deprivation in the Neo-Adjuvant Setting

Immunotherapy is a highly effective treatment for many cancers, but has yet to be optimized for prostate cancer. This is thought to be due in large part, to a lack of anti-cancer immune cells entering the tumors. In prostate cancer, treatment with androgen deprivation therapy (ADT) has been shown to increase the number of immune cells in prostate tumors. However, both anti-tumor T cells and immune-suppressive T cells (called Tregs) increase in number after ADT. Matthew Dallos hypothesizes that this increase in Tregs may profoundly limit anti-tumor immunity, and proposes targeting Tregs as a promising clinical strategy. In this project, Dr. Dallos will initiate a randomized phase 2 clinical trial to test whether adding a Treg-targeting drug (CTLA-4-nf) to ADT can improve anti-tumor immune responses, compared with ADT alone, in men with high-risk localized prostate cancer. Patients will then undergo radical prostatectomy to remove the primary tumor. The impact of these treatments on immune cell types and activities in will be determined in tumor samples from patients on the trial. If successful, this project will result in an effective new immunotherapy and hormone therapy combination for men with prostate cancer.