Metastatic renal cell carcinoma (RCC) is an advanced kidney cancer with few treatment options and a five‑year survival rate below 17%.

With support from CIRM, Allogene Therapeutics is developing ALLO‑316, an allogeneic CAR‑T cell therapy that targets CD70, a protein highly expressed on clear cell renal cell carcinoma (ccRCC) tumors. This approach builds on the success of CAR‑T therapies in blood cancers.

The FDA recently granted ALLO‑316 a Regenerative Medicine Advanced Therapy (RMAT) designation, highlighting its potential to meet a critical unmet need. Early Phase 1 TRAVERSE trial results show encouraging response rates and deepening anti‑tumor activity, marking an important step forward.

CIRM spoke with John LeGall, MD, the principal investigator for ALLO‑316 and a pediatric hematologist/oncologist, to discuss the therapy’s development and the importance of advancing this research.

Can you provide an overview of your research?

Dr. LeGall: Allogene received a $15 million CIRM grant to support the ongoing Phase 1 TRAVERSE trial of ALLO‑316, an allogeneic CAR T therapy targeting CD70 in patients with advanced or metastatic renal cell carcinoma (RCC). Metastatic RCC is the most common kidney cancer worldwide, and patients have few options once checkpoint inhibitors and targeted therapies fail. The five‑year survival rate for advanced kidney cancer remains below 17%.

Although the data is early, Phase 1 studies have shown remarkable responses with ALLO‑316. We believe ALLO‑316 could become a powerful option for patients with advanced RCC who have exhausted available treatments. The CIRM grant allows us to study this therapy in more patients and advance its development for those most likely to benefit.

How would you explain your research to someone who isn’t a scientist?

Dr. LeGall: We are developing a drug to treat cancerous tumors, including advanced kidney cancer. Unlike conventional drugs, our therapy is a “living drug.” We take white blood cells from a healthy donor and engineer them to target CD70, a protein found on kidney cancer cells. After manufacturing, the final product becomes an allogeneic CD70 CAR T engineered to find and kill these cancer cells. The CAR T cells can also multiply in the body, helping eliminate cancer throughout the system, much like natural white blood cells fight infection.

This research is exciting because a therapy like this may unlock long‑term cancer control for patients with solid tumors after a single treatment. This trial will evaluate the allogeneic CD70 CAR T therapy in patients with advanced kidney cancer to identify who is most likely to benefit.

What is the most exciting or significant finding so far?

Dr. LeGall: Many patients have had tumor lesions disappear after receiving a single treatment with allogeneic CD70 CAR T cells.

Can you share a defining moment in your life that led you to pursue this research?

Dr. LeGall: I dedicated myself to the field of cell therapy because I wanted to pursue treatments that had the potential to cure patients when they were out of options. I saw many patients and their families struggle with the challenges of multiply relapsed hematologic and solid tumor malignancies, and that struggle inspired me to pursue the development of new treatments that could lead to a cure. One patient I had was a literal fighter, both in the octagon and against fires. He was recently married when his leukemia unfortunately returned. He was solemn but tough in the face of adversity and was keen to pursue a last shot at remission. I cared for him as he pursued an investigational CAR T therapy – the last treatment option available to him. The therapy likely extended his life for 6 months – and while it was not the cure we had hoped for – both he and his family greatly appreciated our efforts. After that experience, the need to continue to do better for patients and create more opportunities for a cure came to the forefront for me. So, here I am, nine years later, still working to improve CAR T products and make them accessible to more patients and families.

Have there been any unexpected moments of joy or frustration during the research process?

Dr. LeGall: When a patient, who otherwise has no options for treatment, has the courage to sign up to try a new therapy in their fight against cancer, I always find myself incredibly inspired. When that patient manages to substantially extend their life or “feel good” for the first time in years, there is joy and elation knowing that years of work is making a meaningful difference for patients. The team at Allogene is focused on trying to achieve that joy as often as possible.

What is one key message you want to tell the public about your research?

Dr. LeGall: Engineering the immune system to directly fight cancer with CAR T cells has been curative in hematologic (blood) cancers, and we hope to deliver on that promise to patients with solid tumors like advanced kidney cancer. 

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To learn more about Allogene’s recent RMAT designation, read here.