CAR-T Meeting 2026 | Advancing CAR T-cell therapy in T-ALL: promising targets being explored

So there’s been quite a lot of changes in the field of CAR T-cell therapy for T-ALL, I guess, in the last five years or so. And the antigen that’s really come out as the leading antigen at the moment is CD7. So we now have a number of published trials of CD7 CAR T-cell from around the world, both phase one and phase two trials, both of autologous CD7 targeting CAR T-cells and allogeneic targeting CD7 CAR T-cells. And at the moment, one strategy or another hasn’t really emerged as a lead candidate at the moment. So the CD7 CAR-T trial data has been really exciting for the field, particularly for T-ALL because I guess it’s really shown a proof of principle that T-ALL blasts are just as susceptible to CAR-T targeting as B-ALL. And obviously we’ve seen really revolutionary advances in the treatment of B-ALL and we really hope to replicate that for patients with T-ALL. So for us in the field, the CD7 data has been really exciting because what all the trials have really shown, whether they’re autologous or allogeneic, what methods of manufacture they’ve used, they’ve all shown these really high initial complete response rates and really being able to achieve very great depth of response. So putting people into kind of MRD negative responses, particularly in bone marrow disease. 

But while that’s been very exciting, there’s a number of limitations with the CD7 CAR that have begun to emerge as we’ve got more advanced clinical data from some of these trials. So the first I would say really is that these responses do not appear to be durable. So the vast majority of patients in these trials have progressed to an allogenic stem cell transplant after their CD7 CAR. Now that has been largely because of the kind of T lymphocyte depleting effect of a CD7 CAR T-cell. So most patients go into a state of T-cell aplasia and obviously it’s very toxic, and patients are at risk of a lot of opportunistic infections, and so the stem cell transplant really is used as a means of rescuing patients from that T-cell aplasia and resetting their immune system. But what we’ve seen in the minority of patients who haven’t proceeded to a transplant is that a large proportion of those patients seem to relapse after their CD7 CAR. And that can be with CD7 positive or CD7 negative disease. 

So I think the data on the CD7 CAR from around the world is very exciting. I think there’s still a way to go to improve a CD7 CAR. And at UCL, we’re interested in different approaches to try to overcome some of the issues for T-ALL. So in my talk yesterday I spoke about two antigens that we’ve been developing. One is a CCR9 targeting CAR and one is a CD21 targeting CAR. These are what we would call T lymphoblast restricted antigens in that they are expressed on T-ALL but we don’t think they’re expressed on the majority of normal T-cells. So we hope that our CCR9 and CD21 targeting CARs will be effective against T-ALL without the same T-cell aplasia and toxicity that is being seen with the CD7 and other pan-T-cell targeting CARs.

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