CAR-T Meeting 2026 | Challenges associated with developing CAR T-cell therapies for T-ALL and the need for better targets
In this video, Nicola Maciocia, MBChB, PhD, University College London Hospitals NHS Foundation Trust, London, UK, discusses the challenges of developing CAR T-cell therapy for T-cell acute lymphoblastic leukemia (T-ALL). She highlights the importance of identifying better targets that are specific to leukemic cells and not expressed on normal T-cells to minimize toxicity and potentially achieve a standalone cure without the need for consolidative stem cell transplantation. This interview took place at the EBMT-EHA 8th European CAR T-cell Meeting, held in Palma de Mallorca, Spain.
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Transcript
So, there are a number of specific challenges for developing CAR T-cell therapy for T-ALL. One, as I mentioned in my talk yesterday, was the availability of good antigens. So at the moment, CD7, as I said, is the target that most people have been going after, but this is what we call a pan-T-cell target: it’s on all T-ALL, but it’s also on all normal T-cells...
So, there are a number of specific challenges for developing CAR T-cell therapy for T-ALL. One, as I mentioned in my talk yesterday, was the availability of good antigens. So at the moment, CD7, as I said, is the target that most people have been going after, but this is what we call a pan-T-cell target: it’s on all T-ALL, but it’s also on all normal T-cells. So that means it is very toxic, and targeting these antigens leads to issues with manufacturing the CAR T-cells. So you do need to, in most cases, do something during manufacture to remove CD7 from the T-cells to make the CAR T-cells, whether that’s genetic disruption or protein-based downregulation of surface CD7. So that adds complexities to the manufacture of the CAR-T.
There are also issues with depleting a patient’s T-cells and causing quite an immunotoxic therapy. And I think that is the case with these CD7, CD5 targeting CAR T-cells. I think to really get therapy that is effective, but minimally toxic for patients, which is what we want to aim for, we need to find better targets that are largely just expressed on the leukemic cells without expression on normal T-cells. Ideally, we would achieve a standalone cure for patients just with CAR T-cell therapy without reliance on a consolidative transplant, which has its own morbidity and mortality associated with it for patients who’ve already undergone years of very intensive chemotherapy and already have had a transplant. So for me, I think identifying good targets that are not going to be toxic for patients is the key for us developing an effective and less toxic therapy.
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