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CAR33-NK cells are an experimental adoptive cell therapy consisting of primary natural killer (NK) cells genetically engineered to express a second-generation chimeric antigen receptor (CAR) targeting the CD33 antigen, which is highly expressed on acute myeloid leukemia (AML) blasts. To enhance efficacy and overcome immune suppression within the tumor microenvironment, these cells are often further modified using CRISPR/Cas9 to disrupt the *KLRC1* gene, which encodes the inhibitory receptor NKG2A. This dual modification prevents the interaction between NKG2A and its ligand HLA-E (often overexpressed on AML cells), thereby bypassing a critical immune checkpoint that typically impairs NK cell-mediated killing. Preclinical studies have demonstrated that these dual-modified cells (CAR33-KLRC1ko-NK) exhibit superior antileukemic activity and prolonged survival in xenograft models compared to standard CAR-NK cells.
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