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 previous 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.