AUTHOR=Liu Fengqin , Miao Xia , Han Lu , Song Xiao TITLE=Advances in CAR-NK cell therapy for lung cancer: is it a better choice in the future? JOURNAL=Frontiers in Oncology VOLUME=Volume 14 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1390006 DOI=10.3389/fonc.2024.1390006 ISSN=2234-943X ABSTRACT=Lung cancer remains one of the leading causes of cancer-related mortality worldwide, necessitating the development of innovative therapeutic strategies. Chimeric Antigen Receptor (CAR) Natural Killer (NK) cell therapy represents a promising advancement in the field of oncology, offering a novel approach to target and eliminate tumor cells with high specificity and reduced risk of immune-related adverse effects. This paper reviews the mechanism, potential targets, and recent advances in CAR-NK cell therapy for lung cancer, including the design and engineering of CAR-NK cells, preclinical studies, and the outcomes of early-phase clinical trials.We highlight the unique advantages of using NK cells, such as their innate ability to recognize and kill cancer cells and their reduced potential for inducing graft-versus-host disease (GvHD) and cytokine release syndrome (CRS) compared to CAR-T cell therapies. Results from recent studies demonstrate significant antitumor activity in lung cancer models, with improved targeting and persistence of CAR-NK cells observed in vitro and in vivo. Finally, we discuss the challenges in optimizing CAR-NK cell therapies, including the potential resistance mechanisms. The paper concludes with an outlook on the future directions of CAR-NK cell research and its implications for lung cancer treatment, emphasizing the importance of continued innovation and collaboration in the field.