iwAL 2025 | Insights into WU-CART-007: an off-the-shelf CAR-T therapy for T-cell malignancies
John DiPersio, MD, PhD, Washington University School of Medicine, St. Louis, MO, shares insights into the challenges of treating T-cell malignancies with bispecific antibody therapy, highlighting the need to modify or delete antigens to prevent fratricide and ensure targeted killing of malignant cells. He then shares insights into WU-CART-007, an anti-CD7 allogeneic CAR T-cell product, which offers a promising solution without graft-versus-host disease (GvHD) complications. This interview took place at the 7th International Workshop on Acute Leukemias (iwAL 2025), held in Washington, DC.
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Transcript
One of the things, you know, almost in every disease you can think about an option of CAR-T’s as a bispecific. So you target malignancy, and then the other end of the molecule targets the T-cell receptor. And so you bring a T-cell, an endogenous T-cell, towards a tumor cell using this bispecific reagent. So this applies, this can be used for every solid tumor or liquid malignancy, with the exception of T-cell malignancies, because the other end of the molecule engages normal T-cells...
One of the things, you know, almost in every disease you can think about an option of CAR-T’s as a bispecific. So you target malignancy, and then the other end of the molecule targets the T-cell receptor. And so you bring a T-cell, an endogenous T-cell, towards a tumor cell using this bispecific reagent. So this applies, this can be used for every solid tumor or liquid malignancy, with the exception of T-cell malignancies, because the other end of the molecule engages normal T-cells. And T-cell malignancies have the same kind of antigens on them as normal T-cells. And so you’d be targeting normal T-cells and T-cell malignancies with a bispecific therapy. So you get a lot of fratricide, and you basically just knock out all your T-cells. And they may exceed the number of malignant cells dramatically, so you may not even be able to get to your malignant cells. So you have to use CAR-T cells. And so the CAR T-cells, you have to delete or modify the antigen in the CAR-T so that it’s not there. You have to get rid of it because it can’t be there because you’re going to target that same antigen in the malignant T-cell. So that requires some kind of either genetic deletion of that antigen, like CD7. So you take CD7 out of the T-cells and then put the CAR in them to CD7. So suddenly the CAR to CD7 cannot kill itself because that CD7 is no longer present in the CAR T-cells and it only kills the CD7-positive tumor cells. Or you can modify the endogenous antigen so that it’s present but that the CAR-T doesn’t recognize it so there’s no fratricide. So, in the case of WU-CAR-007, it is an allogeneic CAR-T. So, it’s an off-the-shelf reagent in which the T-cell receptor has been disabled or deleted so that my T-cells can be used to treat anybody without graft-versus-host disease complication. And the endogenous target CD7 has been deleted as well. So there’s no CD7 and no T-cell receptor. And then we put a CAR into those cells. And now these T-cells can be used to treat 100 different patients. And so from one collection, when we then take out the TCR and the CD7 and put a CAR into CD7, we can collect enough T-cells that are genetically modified from a single donor to treat 100 patients. And so obviously the economics of CAR-T cell therapy currently will change dramatically. So normally it’s $1 million for one autologous product going into one patient. In this case, you get one unrelated donor to collect enough cells once to treat 100 patients. So the economics should be vastly improved. It depends upon how much these companies charge for these products will be the real test, I think. Thank you.
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