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iwCLL 2025 | A tandem CD19/ROR1 CAR-NK to overcome apoptotic resistance in CLL
In this video, Matthew Davids, MD, Dana-Farber Cancer Institute, Boston, MA, provides insight into the development of a tandem CD19/ROR1 CAR-NK product for the treatment of chronic lymphocytic leukemia (CLL). This novel construct has shown promising in vitro activity and is being further explored in in vivo mouse models, with Dr Davids hoping that this off-the-shelf approach will one day be taken to the clinic. This interview took place at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2025 in Krakow, Poland.
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Transcript
So we’re very excited at this iwCLL meeting to be presenting for the very first time some early data from the laboratory side on our CAR-NK product in CLL that we’ve been developing over this past year. So we know that CAR-T in CLL has relatively minimal benefit for many patients, and yet there is a subset of patients who have durable benefit and CR. One of the reasons we think that CAR-T is impaired in CLL is due to the immune dysfunction of T-cells in this disease...
So we’re very excited at this iwCLL meeting to be presenting for the very first time some early data from the laboratory side on our CAR-NK product in CLL that we’ve been developing over this past year. So we know that CAR-T in CLL has relatively minimal benefit for many patients, and yet there is a subset of patients who have durable benefit and CR. One of the reasons we think that CAR-T is impaired in CLL is due to the immune dysfunction of T-cells in this disease. And so we’ve decided to take a different approach by using an off-the-shelf NK CAR approach. We’ve engineered a new dual construct that includes CD19 and ROR1 to target two key antigens in CLL cells. And for the first time at this meeting, we’ll be presenting the in vitro data suggesting this dual CAR-NK is very active in killing CLL cells in vitro and that it also induces activation through Wnt signaling. And this actually has a pathophysiologic effect because of the ROR1 dependence of CLL. So we think it sort of has a dual effect of killing CLL cells. We’re excited that this preclinical data has now led to in vivo mouse model data that we’re just starting to get underway now. And we’re hoping if that looks promising, this is something that could eventually come to the clinic.
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Disclosures
Consulting: AbbVie, Adaptive Biotechnologies, Ascentage Pharma, AstraZeneca, BeiGene, Bristol-Myers Squibb, Eli Lilly, Galapagos, Genentech, Genmab, Janssen, Merck, MEI Pharma, Nuvalent, Schrödinger; Research Support: Ascentage, AstraZeneca, MEI Pharma, Novartis.
