Evaluating P-PSMA-101 CAR T Cells for Advanced Prostate Cancer
Slovin SF, Gao X, Wei XX, et al. Phase I Trial of P-PSMA-101 CAR T Cells in Patients With Metastatic Castration-Resistant Prostate Cancer. Clinical Cancer Research. 2026; (doi: 10.1158/1078-0432.CCR-25-3052).
While evidence suggests that increasing the share of stem cell-like memory T cells (TSCM) in chimeric antigen receptor (CAR) T-cell products might support immunotherapy for solid tumors, a Phase I trial yielded mixed results. Researchers used P-PSMA-101, an autologous TSCM-rich CAR T-cell construct targeted at prostate-specific membrane antigen, to treat 33 patients with metastatic castrate-resistant prostate cancer. Outcome results revealed both anti-tumor activity and durable responses, with 7 patients registering a decline of 50% or more in prostate-specific antigen and 2 patients achieving declines exceeding 90% and sustained remission. Overall, 20 patients exhibited stable disease and 7 maintained disease stability for 3 months or longer. Researchers reported that robust expansion of P-PSMA-101 CAR T cells was associated with toxicity, including cytokine release syndrome in 20 patients — three of whom experienced grade 3 or higher severity — and one fatal event.