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iwAL 2025 | Perspectives on the promise and challenges of NK cell therapies in AML
John DiPersio, MD, PhD, Washington University School of Medicine, St. Louis, MO, briefly discusses the challenges and potential of using natural killer (NK) cells as an off-the-shelf therapeutic approach in acute myeloid leukemia (AML). Dr DiPersio notes that while NK cells have appeal due to their ability to avoid cytokine release syndrome (CRS) and graft-versus-host disease (GvHD), their persistence and genetic manipulation have proven difficult, leading to limited case studies. This interview took place at the 7th International Workshop on Acute Leukemias (iwAL 2025), held in Washington, DC.
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Transcript
I think the issue with CAR-T’s versus these other effector cells is that we still have not figured out how to make NK cells really expand and persist like T-cells. But on the other hand, if you could, since they don’t seem to elicit the same kind of CRS, and they’re an off-the-shelf reagent where you can use allo products, they have lots of appeal – off-the-shelf allo products, no GvHD, no CRS...
I think the issue with CAR-T’s versus these other effector cells is that we still have not figured out how to make NK cells really expand and persist like T-cells. But on the other hand, if you could, since they don’t seem to elicit the same kind of CRS, and they’re an off-the-shelf reagent where you can use allo products, they have lots of appeal – off-the-shelf allo products, no GvHD, no CRS. The problem is nobody’s been able to consistently get them to persist and work effectively, and they’re very hard to genetically manipulate too. And so, the end case studies that have been done have been done starting with induced pluripotent stem cells (iPSCs) that have been differentiated into NK cells. The primary NK cell stuff has been underdeveloped, I think, because they’re in general hard to get and hard to transduce and hard to show that they persist after they’re infused and expand and kill targets. But someone’s going to figure it out for sure.
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