CD70-targeted allogeneic CAR T-Cell therapy for clear cell renal cell carcinoma.

Allogeneic chimeric antigen receptor (CAR) T-cell therapy is a promising yet underexplored treatment for clear cell renal cell carcinoma (ccRCC), potentially more effective than existing treatment options. This review compares several ongoing preclinical and clinical trials using CAR T-cell therapy. This review discusses the development of CAR T-cell therapy in ccRCC, covering four significant themes: (1) optimizing therapeutic efficacy through combination strategies, (2) the translation pathway from preclinical development to clinical application, (3) safety and toxicity management, and (4) immune response modulation in the tumor microenvironment. Finally, this review highlights opportunities to overcome current limitations and guide future therapeutic approaches. We conducted a structured review of existing research using the PubMed and Google Scholar databases from the past five years, compiled relevant studies on CAR T-cell therapies for ccRCC, and categorized them into four key themes, which were then cross-analyzed to identify trends, challenges, and emerging limitations. Development of universal CAR T-cells may be more affordable, more accessible, and better administrable in less time with fewer mechanical failures than autologous CAR T-cell therapy. Some challenges persist, including patient toxicities, depletion of CAR T-cells in vivo, and an immunosuppressive tumor microenvironment.