Renal cell carcinoma (RCC), especially clear cell RCC, is generally considered an immunotherapy-responsive cancer. Recently, the prognosis for patients with locally advanced and metastatic RCC has significantly improved with the regulatory approvals of anti-PD-1/PD-L1/CTLA-4 immune checkpoint inhibitor (ICI)-based regimens. Yet in most cases, RCC will remain initially unresponsive to treatment or will develop resistance over time. Hence, there remains an unmet need to understand what leads to ICI resistance and to develop novel immune and nonimmune treatments to enhance the response to ICIs. In this review, we highlight recently published studies and the latest clinical studies investigating the next generation of immune approaches to locally advanced and metastatic RCC beyond traditional ICIs. These trials include cytokines, gut microbiota-based therapies, novel immune checkpoint agents, vaccines, and chimeric antigen receptor T cells. These agents are being evaluated as monotherapy or in combination with traditional ICIs and will hopefully provide improved outcomes to patients with RCC soon.
Human vaccines & immunotherapeutics. 2023 Nov 10 [Epub]
Albert Jang, Jake N Lichterman, Jeffrey Y Zhong, Jonathan E Shoag, Jorge A Garcia, Tian Zhang, Pedro C Barata
Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA., Division of Hematology and Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA., Division of Solid Tumor Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA., Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.