Jacobs MT, Wong P, Zhou AY, et al. Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer. Clinical Cancer Research. 2023; (doi: 10.1158/1078-0432.CCR-23-0156).
Researchers have identified strategies that promise to improve natural killer (NK) cells as a cellular therapy for head and neck squamous cell carcinoma (HNSCC). At present, NK cells often are dysfunctional in this patient population, signaling a need for stronger cell responses against the disease. Preclinical investigation found that compared with conventional NK cells, memory-like (ML) NK cells increased production of interferon alpha and tumor necrosis factor and exhibited both short- and long-term killing of HNSCC cell lines and primary targets. Through the addition of tumor targeting with cetuximab, the enhanced effects of ML NK cells were only compounded. ML NK cells engineered to express anti-EphA2 (Erythropoietin-producing hepatocellular receptor A2) chimeric antigen receptor (CAR) were more effective against HNSCCs than conventional NKs with EphA2 CAR engineering. The results support advancing studies of ML NKs — in combination with either cetuximab or EphA2 CAR — into the clinical phases with human HNSCC patients.