Integration of humanized ROBO1 CAR in PD-1 locus in natural killer cells delivers synergistic tumor-killing effect against non-small cell lung cancer



Summary

Engineering natural killer (NK) cells with chimeric antigen receptors (CARs) targeting tumor-associated antigens holds promise for cancer immunotherapy. This research explores integrating a humanized ROBO1-targeting CAR into the PD-1 locus of NK cells. This strategy not only directs NK cell cytotoxicity towards ROBO1-expressing non-small cell lung cancer (NSCLC) cells but also disrupts the PD-1 inhibitory pathway, enhancing anti-tumor activity. The resulting NK cells demonstrated superior and synergistic tumor-killing effects against NSCLC in vitro and in vivo compared to NK cells expressing the ROBO1-CAR without PD-1 disruption. This dual-action approach presents a novel strategy for improved NK cell-based immunotherapy for NSCLC.

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