CAR-NK cell therapy for hematological malignancies

Chimeric antigen receptor (CAR)-natural killer (NK) cells represent a novel cell therapy platform distinguished from CAR-T cells by their more favorable safety profile, easier off-the-shelf allogeneic manufacturing and consequent scalability, and their innate cytotoxicity without needing prior sensitization. CAR-NK cells derived from a variety of sources have been used against hematologic malignancies in several clinical trials, showing significant therapeutic responses and efficacy without severe adverse effects. Limitations that are being addressed in CAR-NK cell therapy include challenges regarding NK cell persistence in vivo, metabolic bottlenecks, and tumor-coopted immunosuppressive mechanisms that induce NK cell exhaustion. This review synthesizes current trends and innovations in CAR-NK cell engineering, examines the biological and technical challenges encountered in the clinical setting, outlines targeted preclinical approaches being implemented, and introduces recent early-phase clinical trials in the pipeline. Summatively, we highlight the rapidly advancing and transformative potential of CAR-NK cell therapy for treating hematological cancers.