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0The paper explores the development and clinical application of chimeric antigen receptor (CAR)-engineered natural killer (NK) cells as a transformative immunotherapy for cancer. While CAR-T cell therapy has succeeded in treating blood cancers, it faces hurdles in solid tumors due to high toxicity and complex manufacturing requirements. In contrast, CAR-NK cells offer a safer, more accessible "off-the-shelf" alternative that leverages the innate ability of NK cells to destroy malignant tissues without causing severe side effects like graft-versus-host disease. Despite this potential, the sources highlight significant obstacles in treating solid tumors, including the immunosuppressive tumor microenvironment, physical barriers to infiltration, and limited cell persistence. To address these bottlenecks, researchers are investigating novel engineering strategies such as cytokine armoring, metabolic reprogramming, and combination therapies with radiation or chemotherapy. Ultimately, the text synthesizes recent preclinical breakthroughs and early-phase clinical trials to underscore the evolving landscape of NK-based therapeutics across various human malignancies.
References:
Manzar GS, Hasan MF, Moore M, Tiberti S, Osorio NP, Basar R, Daher M. Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions. Cell Rep Med. 2026 Jun 2881. doi: 10.1016/j.xcrm.2026.102881. Epub ahead of print. PMID: 42349415.
