Chimeric antigen receptor natural killer (CAR-NK) cells: from preclinical promise to clinical reality in cancer immunotherapy

Abstract

Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents an emerging frontier in cancer immunotherapy. CAR‐NK cells offer the potential for “off‐the‐shelf” treatments with a favorable safety profile, due in part to their innate capacity for HLA‐unrestricted tumor targeting and an absence of graft‐versus‐host disease. Landmark clinical studies using cord blood–derived CAR-NK cells and another employing iPSC-derived CAR-NK cells have reported impressive response rates, durable remissions, and minimal toxicity. Furthermore, a growing landscape of ongoing clinical trials is exploring innovative strategies to enhance persistence, overcome solid tumor challenges, and prevent antigen escape. These advances collectively underscore the potential of CAR-NK therapies to revolutionize cancer treatment while addressing limitations associated with current CAR-T cell approaches.