CAR-NK immunotherapy and cancer therapy

Although CAR-T has been applied in clinic, quite a lot of side effects, such as off-target, cytokine release syndrome (CRS) etc., pose a great restriction in their further clinical application [47]. Based on natural killer (NK) cells, CAR-NK cell therapy is much safer than CAR-T therapy and becomes a good candidate for targeting and combating solid tumors [48,49]. Based on the four generation of CAR, CARs in CAR-NK are designed with the addition of personalized proteins, such as DNAX-activation protein (DAP) 12 and NKG2 member D (NKG2D), which show great anti-tumor activity in acute myeloid leukemia (ALL), osteosarcoma, and prostate tumors [50-52]. Therefore, CAR-NK cells not only have the ability of CAR to specifically recognize antigen-expressing tumors, but also can destroy tumors via NK cell receptors. To date, numerous CAR-NK cell therapies have been used for anti-tumor therapy in clinical trials (Table 3).