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).
We present a neoadjuvant clinical trial testing whether an afucosylated anti-CTLA-4 antibody (BMS-986218) with ADT is safe, feasible, and reduces TI-Treg frequencies. This single-center, two-arm, open-label study randomizes 24 men with high-risk localized PCa to ADT with or without BMS-986218 prior to radical prostatectomy. Treatment is well tolerated and feasible. Mechanistic studies reveal reductions in TI-Treg frequencies correlate with CD16a/FCGR3A on tumor macrophages, dendritic cell (DC) modulation, and augmented T cell priming following BMS-986218 treatment. Depth of Treg inhibition and increased DC frequencies are associated with improved clinical outcomes. Overall, this study supports the feasibility and biological activity of neoadjuvant ADT + Fc-enhanced anti-CTLA-4 in high-risk PCa. Trial is registered at clinicaltrials.gov (NCT04301414).
Cell reports. Medicine. 2026 Feb 26 [Epub ahead of print]
Casey R Ager, Aleksandar Obradovic, Patrick McCann, Matthew Chaimowitz, Alexander L E Wang, Neha Shaikh, Parin Shah, Samuel S Pan, Caroline J Laplaca, Renu K Virk, Jessica C Hill, Collin Jugler, Grace DeFranco, Nilika Bhattacharya, Kade R Copple, Phuong Nguyen, Howard I Scher, Guarionex Joel DeCastro, Christopher B Anderson, James M McKiernan, Catherine S Spina, Mark N Stein, Karie Runcie, Charles G Drake, Andrea Califano, Matthew C Dallos
Department of Medicine, Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Immunology, Mayo Clinic Arizona, Phoenix, AZ 85054, USA; Department of Urology, Mayo Clinic Arizona, Phoenix, AZ 85054, USA. Electronic address: ., Department of Systems Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA., Department of Radiation Oncology, Columbia University Irving Medical Center, New York, NY 10032, USA; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA., Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA., Department of Urology, Columbia University Irving Medical Center, New York, NY 10032, USA., Department of Pathology, Columbia University Irving Medical Center, New York, NY 10032, USA., Department of Immunology, Mayo Clinic Arizona, Phoenix, AZ 85054, USA., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Department of Radiation Oncology, Columbia University Irving Medical Center, New York, NY 10032, USA., Department of Medicine, Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY 10032, USA., Department of Medicine, Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Urology, Columbia University Irving Medical Center, New York, NY 10032, USA., Department of Systems Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biochemistry & Molecular Biophysics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA; Chan Zuckerberg Biohub New York, New York, NY 10027, USA., Department of Medicine, Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY 10032, USA; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: .