ASH 2025 | Developing and testing a tandem CD19/ROR1 CAR-NK to overcome apoptotic resistance in CLL

One of the other challenges in CLL is that there’s inherent T-cell dysfunction in the disease. And we’ve seen this with CAR-T cell therapies, which are often very effective in other B-cell non-Hodgkin lymphomas. But in CLL, we see relatively low rates of complete remission. And although there’s a lot of promising new strategies with CAR-T, my laboratory group has developed a new strategy that’s an alternative to CAR-T that we’re exploring now in the lab to hopefully bring someday to the clinic for CLL. And this is a CAR-NK-based strategy, so natural killer cells. There is a precedent for this – a group at MD Anderson had previously treated a small number of CLL patients with a CAR-NK and saw activity. That was a CD19-directed CAR product. So we’ve engineered, in collaboration with Rizwan Romee at Dana-Farber, a CD19/ROR1 dual CAR-NK product that we’ve now done some initial in vitro testing on. And we showed at this meeting promising in vitro data, as well as some early in vivo data in mouse models, suggesting that this dual CAR can be very effective in mouse models of CLL. This is a work in progress still. We’re generating additional in vitro and in vivo data, but I think if we can confirm these promising initial results, we hope to be able to get this into an early phase clinical trial relatively soon.

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