Metastatic renal cell carcinoma (RCC) is an advanced form of kidney cancer with few treatment options and a five-year survival rate of less than 17%.
With funding support from CIRM, Allogene Therapeutics is developing ALLO-316, an allogeneic CAR-T cell therapy which targets CD70—a protein highly expressed on clear cell renal cell carcinoma (ccRCC) tumors. This innovative approach builds on CAR-T cell therapies’ revolutionary impact in treating blood cancers.
Recently, ALLO-316 received the FDA’s Regenerative Medicine Advanced Therapy (RMAT) designation, underscoring its potential to address a critical unmet need. Early results from the Phase 1 TRAVERSE trial showed encouraging response rates and deepening anti-tumor activity, signaling a critical step forward.
CIRM connected with the principal investigator behind ALLO-316, pediatric hematologist/oncologist John LeGall, MD, to share his insights on the development of the therapy and the importance of advancing this research.
CIRM: Can you provide an overview of your research?
Dr. LeGall: Allogene was awarded a $15 million CIRM grant to support our ongoing Phase 1 TRAVERSE trial evaluating an allogeneic CAR T targeting CD70 (ALLO-316) in patients with advanced or metastatic renal cell carcinoma (RCC). Metastatic RCC is the most common kidney cancer globally and there are limited treatment options after treatments with checkpoint blockers and targeted therapy have failed. The five-year survival rate for patients with advanced kidney cancer is less than 17%.
Although the data is preliminary, we have observed remarkable responses after treatment with ALLO-316 in Phase 1 studies. We believe ALLO-316 has the potential to be a powerful therapeutic option for patients with advanced RCC who have exhausted all available treatments. This grant from CIRM is helping us explore this treatment in more patients, so we can move its development forward in those who are most likely to benefit.
CIRM: 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 more conventional drugs, what we are developing is a “living drug.” We take a healthy person’s fresh white blood cells (part of the body’s immune system) and engineer them to target a protein called CD70, which appears on the surface of kidney cancer cells. After it has been manufactured, this final product is now an allogeneic (meaning from another healthy person) CD70 CAR T that has been engineered to attack and kill this specific type of kidney cancer cell. The CAR T cells also will continue to grow in number to eliminate kidney cancer cells throughout the body, similar to how your own white blood cells work to protect you from infections. What’s exciting about this research is that this type of treatment may be the key to unlocking long-term cancer cures in patients with malignant solid tumors after just a single treatment. This specific trial will evaluate the allogeneic CD70 CAR T product in patients with advanced kidney cancer to help better understand which patients are most likely to benefit.
CIRM: 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.
CIRM: 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.
CIRM: 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.
CIRM: 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.
To learn more about Allogene’s recent RMAT designation, read here.
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- Source: https://blog.cirm.ca.gov/2024/12/10/a-step-forward-in-the-fight-against-advanced-kidney-cancer/