Yulin LAI, Wenzhu CHAI, Bin HUANG, Zhu WANG, Hui LIANG
Journal of Urological Surgery - 2026;13(2):72-79
Renal cell carcinoma (RCC) is a common urologic malignancy with poor outcomes in metastatic disease, despite advances in targeted therapies and immune checkpoint inhibitors. Chimeric antigen receptor (CAR)-engineered cell therapies, particularly CAR-T and CAR-natural killer (CAR-NK) cells, have revolutionized the treatment of hematologic malignancies, but face unique barriers in solid tumors such as RCC, including tumor heterogeneity and an immunosuppressive microenvironment. Using the Trialtrove database with the keywords "CAR" and "oncology: kidney," we identified 44 eligible interventional trials as of June 10, 2025. Most are early-phase and industry-sponsored, and are conducted primarily in China and the United States. CAR-T studies outnumber CAR-NK trials, with cluster of differentiation 70 as the most common target, followed by estimated glomerular filtration rate and programmed cell death protein 1. Combination regimens frequently incorporate lymphodepletion with cyclophosphamide and fludarabine. Preliminary clinical data indicate that CAR therapies for RCC are generally safe and feasible but show limited durable efficacy. Key obstacles include antigen escape and poor persistence of infused cells within the tumor microenvironment. To overcome these challenges, next-generation strategies-such as dual-target CAR constructs, cytokine co-expression (e.g., interleukin-15), and biomarker-guided patient selection-are actively being explored. Regulatory frameworks in the United States and China increasingly support innovation in cellular therapies. Overall, the evolving clinical landscape highlights both the promise and the ongoing challenges of CAR-engineered therapies for RCC, underscoring the need for optimized designs and rational combination approaches to improve patient outcomes.
