Targeting urological cancers with CAR-T cell therapy: current landscape and future directions

BACKGROUND: Urological cancers, including renal, bladder, and prostate cancers, are among the most prevalent solid tumors. The success of chimeric antigen receptor (CAR)-T cell therapy in hematologic malignancies has spurred its exploration for treating urological cancers. MAIN BODY: In the past decade, preclinical studies have demonstrated promising antitumor activity of CAR-T cells against urological cancers. Meanwhile, multiple clinical trials are currently underway to evaluate their safety and efficacy. However, significant challenges impede the efficacy of CAR-T cell therapy in urological cancers, including tumor heterogeneity and antigen escape, the immunosuppressive tumor microenvironment (TME), and treatment-related toxicities. To address these limitations, current research efforts are actively explored on several strategies, such as identifying novel target antigens, engineering CAR structurally optimized, and reversing the immunosuppressive TME. This review systematically summarizes these recent research advances for renal, bladder, and prostate cancers. CONCLUSIONS: Accumulating evidence supports the therapeutic potential of CAR-T cell therapy for urological cancers. To realize its clinical promise, future research needs focus on design of combinatorial strategies, optimizing the balance between efficacy and toxicity, validating findings in larger and more diverse patient cohorts, and developing more precise, individualized treatment regimens.