Fc-enhanced anti-CTLA-4 depletes tumor-infiltrating regulatory T cells to augment immune effects of androgen ablation in high-risk prostate cancer.

ABSTRACT: Despite high rates of post-surgical recurrence in men with high-risk localized prostate cancer (PCa), there is currently no role for neoadjuvant therapy. Tumor infiltrating regulatory T cells (TI-Tregs) limit the antitumor effects of presurgical androgen deprivation therapy (ADT). Therefore, we designed a neoadjuvant clinical trial to test whether Treg depletion via a non-fucosylated anti-CTLA-4 antibody (BMS-986218) is feasible and augments response to ADT. In this single-center, two-arm, open-label study, 24 men with high-risk localized PCa were randomized to ADT with or without BMS-986218 prior to radical prostatectomy. Treatment was well tolerated and feasible. Mechanistic studies indicated BMS-986218 depleted TI-Tregs by engaging CD16a/FCGR3A on tumor macrophages, modulated den

SUBMITTER: Ager CR 

PROVIDER: S-EPMC11419205 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature