Synergizing CAR with memory-like NK cells

Abstract

Natural killer (NK) cells are crucial for combating the tumor growth and spread of cancer. The receptors which inhibit and activate NK cells coordinate to recognize "self" or "missing-self" to determine whether NK cells should be activated to destroy the targets. NK cells exhibit intrinsic memory to haptens and viral infections despite lacking antigen-specific receptors. A combination of Interleukins may create cytokine-induced memory-like (ML) NK cells that respond more vigorously to tumors and lessen symptoms in cancer patients. Meanwhile, chimeric antigen receptors (CAR) have been utilized to modify NK cells. CAR-NK cells have been tested to be more powerful in treating solid tumors and hematological cancers in both pre-clinical and clinical trials. A few recent studies showed that when ML NK cells are armed with CAR, the resulting CAR-ML-NK cells demonstrated better survival in human xenograft models as well as enhanced responses against cancer cells in vitro and in vivo.