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CD33.CAR NK TGFβi is an experimental cell therapy consisting of natural killer (NK) cells engineered to express a chimeric antigen receptor (CAR) targeting CD33, a surface antigen highly expressed in acute myeloid leukemia (AML) blasts. These cells undergo "TGFβ imprinting" (TGFβi) during expansion, a process involving chronic TGFβ stimulation that induces high levels of IFNγ and TNF secretion and confers resistance to TGFβ-mediated immunosuppression within the tumor microenvironment. Developed by researchers at New York Medical College and Nationwide Children's Hospital, this therapy is designed to overcome the limitations of conventional NK cell persistence and potency. Preclinical studies demonstrate that the combination of CD33 targeting and TGFβ imprinting, particularly when augmented by IL-15 receptor agonists like NKTR-255, significantly enhances cytotoxicity and survival in AML models.
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