Non-viral delivery and genome editing for CAR-NK engineering in solid tumors: from ex vivo manufacturing to in vivo reprogramming

Chimeric antigen receptor (CAR)-engineered natural killer (NK) cell therapy has emerged as a promising immunotherapeutic strategy for cancer treatment, offering advantages over CAR-T cells such as a lower risk of cytokine release syndrome and graft-versus-host disease and the potential for off-the-shelf manufacturing. Viral vectors have long served as effective tools for CAR-NK engineering, but their dependence on complex manufacturing procedures, considerable production costs, and the potential risks associated with genomic integration has encouraged increasing interest in non-viral alternatives. Recent advances in genetic engineering technologies have facilitated the development of CAR-NK platforms, particularly through non-viral delivery approaches including electroporation, transposon systems and lipid nanoparticles, while CRISPR-based tools enable targeted genome editing. Meanwhile, an increasing number of clinical trials have begun to evaluate the safety and therapeutic potential of CAR-NK cells in both hematological malignancies and solid tumors. However, challenges such as limited NK-cell persistence, antigen heterogeneity, and the immunosuppressive tumor microenvironment remain. In this review, we summarize recent progress in non-viral CAR-NK engineering strategies, analyze the current landscape of preclinical and clinical trials, and discuss key challenges and future directions for advancing CAR-NK therapy. Collectively, these advances suggest that non-viral engineering technologies may serve as an important technological foundation for next-generation CAR-NK therapies, enabling more flexible ex vivo manufacturing and potentially supporting the future development of in vivo CAR-NK generation strategies for solid tumors.

Abstract from PubMed (PMID 42925903). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.