Phase 1 Trial of Allogeneic CAR-NK Therapy for Metastatic Prostate Cancer

A new clinical trial is exploring allogeneic CAR-NK cell therapy targeting PSMA for patients with metastatic castration-resistant prostate cancer, or mCRPC. This exploratory study (not yet recruiting as of late 2025), aims to assess the safety profile alongside early signs of efficacy in men whose disease has progressed despite hormone suppression and other therapies. Unlike patient-specific CAR-T therapies that demand weeks of custom manufacturing, this approach uses off-the-shelf NK cells from healthy donors, genetically modified to zero in on PSMA, potentially speeding access for those in urgent need.

NK cells bring inherent advantages to the fight against solid tumors like prostate cancer. These innate immune warriors kill cancer cells without needing prior sensitization, and their CAR engineering amplifies this by directing them precisely to PSMA-expressing sites. Preclinical work, including studies with NK-92 cell lines, has shown these modified cells not only shrink tumors but also pair well with checkpoint inhibitors like anti-PD-L1 antibodies to overcome the prostate’s immunosuppressive environment. In mouse models of CRPC, combinations like this have boosted cytotoxicity, reduced PSA levels, and slowed tumor growth far beyond NK cells alone, hinting at real-world potential without the severe cytokine storms sometimes seen in CAR-T treatments.

Clinical trial.