CAR T-Cell Therapy Targeting CAIX/CD70 May Improve Tumor Cell Killing in ccRCC

At the 2025 Kidney Cancer Research Summit, Wayne A. Marasco, MD, PhD, presented on his goal to investigate a chimeric antigen receptor (CAR) T-cell therapy that targets CAIX and CD70, 2 molecules that are overexpressed in clear cell renal cell carcinoma (ccRCC).

CancerNetwork® spoke with Marasco, a professor in the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute, a professor of medicine at Harvard Medical School, and an associate physician in the Division of Infectious Diseases at Brigham and Women’s Hospital, at the conference.

The presentation showed that, when compared with untransduced T cells, dual-targeted anti-CAIX/CD70 CAR T cells showed stagnated tumor growth at 7, 14, 21, and 28 days after treatment.

According to Marasco, the heterogeneous nature of these tumors required that 2 molecules be targeted because by only targeting 1, it is much more difficult to achieve high levels of tumor cell killing.

Transcript:

One of the common features of all solid tumors, but in this case renal cell carcinoma, which is the emphasis of my work, [is that] when we looked at the tumors and went to the pathologists, we sampled 40 or 45 tumors from different patients with different stages of disease and found what we expected to find, which is there’s no single type of tumor in a tumor bed. They are heterogeneous in terms of what they express on the surface and what they look like. What we found was that it’d be very difficult to be able to get 100% tumor cell killing if you just target 1 molecule on the surface. If we were able to target 2 molecules on the surface, we could get over 99% of the cases covered. We decided to build the therapy based on the 2 molecules, CAIX and CD70. I showed data on what the staining looked like in those 45 patients. If you use both of those targets, you can achieve complete coverage of all [patients with] RCC who have a tumor.

Reference

Marasco WA. Redesigning CAR T cells for solid tumors: a new path toward cures of ccRCC. Presented at: 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA.