Therapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors. We also report results from 16 patients with relapsed/refractory ccRCC who received CTX130 in a phase I, multicenter, first-in-human clinical trial. No patients encountered dose-limiting toxicity, and disease control was achieved in 81.3% of patients. One patient remains in a durable complete response at 3 years. Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. These data represent a proof of concept for the treatment of ccRCC and other CD70+ malignancies with CD70-targeted allogeneic CAR T cells.
Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors.
Cancer discovery. 2024 Apr 05 [Epub ahead of print]
Sumanta K Pal, Ben Tran, John B A G Haanen, Michael E Hurwitz, Adrian Sacher, Nizar M Tannir, Lihua E Budde, Simon J Harrison, Sebastian Klobuch, Sagar S Patel, Luis Meza, Mary-Lee Dequeant, Anna Ma, Qiuling Ally He, Leah M Williams, Alissa Keegan, Ellen B Gurary, Henia Dar, Sushant Karnik, Changan Guo, Heidi Heath, Rachel R Yuen, Phuong K Morrow, Neeraj Agarwal, Samer A Srour
Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California., Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Netherlands Cancer Institute, Amsterdam, the Netherlands., Yale School of Medicine, New Haven, Connecticut., Princess Margaret Cancer Centre, University Health Network, Toronto, Canada., University of Texas MD Anderson Cancer Center, Houston, Texas., Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah., CRISPR Therapeutics, Boston, Massachusetts., Formerly employed by CRISPR Therapeutics, Boston, Massachusetts., Division of Medical Onco-logy, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.