Researchers modified natural killer cells with 2B4 and DAP12 co-stimulatory domains, creating CAR-NK cells that demonstrated enhanced cytotoxic programming against CD19-positive cancer cells. Transient dasatinib exposure paradoxically improved these engineered cells' tumor-killing capacity upon drug withdrawal, with 2B4-DAP12 CAR-NK cells showing superior tumor control compared to conventional 4-1BBζ designs in xenograft models. This finding represents a significant departure from traditional CAR-T cell engineering approaches, which have dominated immunotherapy development. NK cells possess inherent advantages including reduced graft-versus-host disease risk and broader applicability across patients, but optimizing their signaling pathways has proven challenging. The 2B4 domain appears particularly suited to NK cell biology, activating cytotoxic programs more effectively than T cell-derived co-stimulatory signals. The dasatinib preconditioning strategy suggests that temporary kinase inhibition may prime NK cells for enhanced subsequent activation, potentially offering a pharmacologic method to boost therapeutic efficacy. While promising, these results require validation in primary NK cells and larger animal models before clinical translation, as immortalized cell lines may not fully recapitulate primary NK cell behavior.