Despite the addition of multiple life-prolonging therapeutic modalities now available to treat patients with mCRPC, the mechanism of action of sipuleucel-T remains unique for patients with advanced prostate cancer. Therefore, maximizing the appropriate clinical utilization of sipuleucel-T in patients with mCRPC within current treatment paradigms is essential.

We previously reported a clinical trial (NCT02499835) evaluating PD-1 blockade combined with an anti-tumor DNA vaccine, pTVG-HP (encoding prostatic acid phosphatase), in patients with metastatic castration-resistant prostate cancer...These findings suggest that patients experiencing irAEs can have immune responses to tumor irrespective of obvious anti-tumor efficacy, at least with these treatments, and underscore the importance of tumor-infiltrating professional antigen presenting cells and T-cell activation for successful immunotherapy. Moreover, our findings suggest that combining vaccines and PD-1 blockade with MDSC-targeting therapies, anti-VISTA, and/or anti-PARP therapies might be further explored.

Given the use of sipuleucel-T as a standard of care backbone, there is emerging interest in combining it with other immunotherapies, hormonal therapies, or chemotherapies to improve its clinical efficacy. This review summarizes past experiences and current knowledge of combining sipuleucel-T with other treatments and explores future approaches to enhance such combinatorial strategies.

P1, N=14, Recruiting, University of Wisconsin, Madison | Not yet recruiting --> Recruiting

P1, N=30, Not yet recruiting, City of Hope Medical Center

Prior to the advent of ICIs, prostate cancer had one of the first approvals for cancer immunotherapy with sipleucel-T, an anti-cancer vaccine...Most notably, clinical trials with bispecific T-cell engagers (BiTEs) targeting tumor antigens like STEAP-1 and KLK2 have shown clinical promise. Moving beyond ICIs may lead to new approaches to alter the prostate cancer tumor immune microenvironment and improve clinical outcomes.

P2, N=26, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Aug 2025 --> Dec 2025

P2, N=400, Recruiting, Dendreon | Not yet recruiting --> Recruiting | Phase classification: P3 --> P2

P1, N=14, Not yet recruiting, University of Wisconsin, Madison

P2, N=26, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Mar 2025 --> Aug 2025

P1, N=13, Recruiting, University of Oklahoma | Trial completion date: Nov 2024 --> Dec 2026 | Trial primary completion date: Nov 2024 --> Jun 2026

P1, N=33, Fujian Medical University Union Hospital; Fujian Medical University Union Hospital