CAR‐NK Cell Biology and Engineering for Solid Tumors, With a Focus on Lung Cancer

ABSTRACT Over the past decade, chimeric antigen receptor (CAR) T‐cell therapy has revolutionized cancer immunotherapy, demonstrating remarkable efficacy in treating relapsed or refractory hematologic malignancies across both pediatric and adult populations. In parallel, CAR‐engineered natural killer (CAR‐NK) cells have emerged as a complementary and promising alternative to CAR‐T therapy, offering several inherent advantages. Unlike CAR‐T cells, CAR‐NK cells operate independently of major histocompatibility complex (MHC) compatibility and are associated with a lower risk of adverse immune reactions. They also provide practical benefits, such as the potential for standardized, “off‐the‐shelf” therapeutic formulations. Consistent and encouraging outcomes have been reported with CAR‐NK cell therapy in hematologic cancers; however, their success against solid tumors remains constrained by multiple challenges, including limited tumor infiltration, suboptimal trafficking, and the immunosuppressive characteristics of the tumor microenvironment. Importantly, lung cancer presents indication‐specific barriers to cellular immunotherapy, including profound inter and intratumo