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ASH 2024 | Improving CAR development to circumvent the challenges presented by AML
Renier Brentjens, MD, PhD, Roswell Park Comprehensive Cancer Center, Buffalo, NY, comments on overcoming the challenges with CAR T-cell therapy development in acute myeloid leukemia (AML), specifically highlighting the need to enhance safety features such as logic-gated approaches that prevent unwanted cell activation. Dr Brentjens emphasizes the importance of first achieving molecular remission in patients before addressing safety concerns. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript
So when you’re going after a target where you have to be careful because normal tissues express the target, there’s an ever-growing body of preclinical literature that really talks about ways that you can enhance the safety of these CAR T-cells, turning them on and off, and having these CAR T-cells be further engineered with these logic-gated approaches where if it encounters a benign cell, it doesn’t turn on an attack...
So when you’re going after a target where you have to be careful because normal tissues express the target, there’s an ever-growing body of preclinical literature that really talks about ways that you can enhance the safety of these CAR T-cells, turning them on and off, and having these CAR T-cells be further engineered with these logic-gated approaches where if it encounters a benign cell, it doesn’t turn on an attack. And if it encounters a malignant cell that’s missing that second target, it attacks and kills. And so there’s a variety of very interesting and very elegant preclinical studies that look to address this issue, not just in AML, but even more, probably more relevantly in solid tumor malignancies that we and others are working on. I think that the first step with myeloid leukemias is to get patients into a molecular remission. We can deal with a lot of the toxicities either with transplants or with immunosuppressive medications. And so I think the first step really is to find a target and be able to eradicate the disease and get the patient through that process. And I think down the line, again, using the CAR acronym, we’ll find ways of putting in seat belts and airbags so that these approaches are safer. We just need to first validate that we can actually eradicate the disease in our patients and then try to improve on the safety moving forward.
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Disclosures
Triumvira, Cargo Tx, CoImmune: Membership on an entity’s Board of Directors or advisory committees; BMS: Research Funding; BMS, Caribou, Sanofi: Other: licensed intellectual property to and collects royalties from; BMS, Atara Biotherapeutics Inc. and was a consultant for Triumvira, Cargo Tx, CoImmune: Consultancy.
