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Review
. 2023 Dec 15;19(3):2276629.
doi: 10.1080/21645515.2023.2276629. Epub 2023 Nov 10.

Immune approaches beyond traditional immune checkpoint inhibitors for advanced renal cell carcinoma

Albert Jang  1   2 , Jake N Lichterman  3 , Jeffrey Y Zhong  2 , Jonathan E Shoag  4 , Jorge A Garcia  2 , Tian Zhang  3 , Pedro C Barata  2
Affiliations
Review

Immune approaches beyond traditional immune checkpoint inhibitors for advanced renal cell carcinoma

Albert Jang et al. Hum Vaccin Immunother. .

Abstract

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.

Keywords: CAR T-cell therapy; Immunotherapy; cytokine; gut microbiota; immune checkpoint inhibitor; interleukin; vaccine.

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Conflict of interest statement

Jonathan E. Shoag received personal fees from Fortec Medical and grants from BMS Foundation. Jorge A. Garcia received personal fees from Pfizer, Aptitude Health, and the US Food and Drug Administration. Tian Zhang received research funding from Acerta, Novartis, Merrimack, AbbVie/StemCentrx, Merck, Regeneron, Mirati Therapeutics, Janssen, AstraZeneca, Pfizer, OmniSeq, Personal Genome Diagnostics, Astellas, and Eli Lilly, served as advisory board member and consultant for Merck, Exelixis, Sanofi-Aventis, Janssen, AstraZeneca, Pfizer, Amgen, BMS, Pharmacyclics, SeaGen, Calithera, QED Therapeutics, Eisai, Aveo, Eli Lilly, Bayer, and Aravive, and received honoraria from MJH Associates, Vaniam, Aptitude Health, and PeerView. Pedro C. Barata received personal fees from BMS, Merck, and EMD Serono, grants from Roche, personal fees from Eisai, Exelixis, Pfizer, Caris Life Sciences, Myovant, and UroToday, and nonfinancial support from Guardant360. All the other authors declare no conflict of interest.

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