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iwCLL 2025 | Strategies being explored to enhance the metabolic function of T-cells in CLL
In this video, Helga Simon-Molas, PhD, Amsterdam University Medical Center, Amsterdam, Netherlands, briefly outlines the strategies being explored to enhance the metabolic function of T-cells in chronic lymphocytic leukemia (CLL). Dr Simon-Molas highlights that inhibition of PI3K signaling has demonstrated efficacy in regulating the metabolism of T-cells from human CLL patients and also in CAR T-cells in mouse models. However, this approach may have detrimental effects on patients, and alternative strategies should be explored. This interview took place at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2025 in Krakow, Poland.
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Transcript
What we have done so far is to block PI3 kinase signaling, which we found to be increased in the T-cells from the patients. That’s a publication from earlier this year that we did together with the group in the Moffitt Cancer Center. And what we see there is that if we block this hyper-signaling, then we can manage to get these T-cells away from the glycolysis pathway and bring them back to the OXPHOS, to the mitochondrial oxidative pathway...
What we have done so far is to block PI3 kinase signaling, which we found to be increased in the T-cells from the patients. That’s a publication from earlier this year that we did together with the group in the Moffitt Cancer Center. And what we see there is that if we block this hyper-signaling, then we can manage to get these T-cells away from the glycolysis pathway and bring them back to the OXPHOS, to the mitochondrial oxidative pathway. This is for now the only strategy that we have proved to be effective, both in T-cells from human CLL patients and also in CAR T-cells that we have used in a mouse model. But because this is a bit of a complex treatment to apply in patients, because PI3K signaling inhibitors also have quite a lot of detrimental effects for patients, if we would use them in the patient, we are thinking about strategies to improve mitochondrial remodeling, for example, boosting lipid metabolism, so something a little bit more tailored to the T-cells, while still sort of preserving the normal cells.
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