Genomic DNA loci in ex vivo engineered Natural Killer cells

Genomic DNA loci in ex vivo engineered Natural Killer (NK) cells represent specific sites within the NK cell genome that are targeted for genetic modification to enhance the efficacy of adoptive cell therapies. These modifications typically involve the use of gene-editing technologies, such as CRISPR-Cas9, to knock out inhibitory genes like CISH, which regulates cytokine signaling, or TGFBR2, which mediates immunosuppression in the tumor microenvironment (PMID: 32518419, PMID: 35132118). Additionally, these loci may serve as integration sites for Chimeric Antigen Receptors (CARs) or cytokines like IL-15 to improve tumor targeting and cell persistence. By precisely altering these genomic regions, researchers can create "off-the-shelf" allogeneic NK cell products with enhanced cytotoxicity and metabolic fitness. The therapeutic goal is to overcome the limitations of primary NK cells, such as short half-life and susceptibility to tumor-induced exhaustion. However, targeting these loci presents challenges, including the risk of off-target mutations and chromosomal translocations that could lead to malignant transformation of the engineered cells (PMID: 30635454).

Other names

NK cell genomic targetsEngineered NK cell DNACRISPR-edited NK cell lociNK cell gene editing sites

Site-specific genomic modification (knockout or knock-in) to enhance effector function, persistence, and resistance to the tumor microenvironment.