Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma

The chimeric antigen receptor-modified immune effector cell (car-t and car-nk) therapies are newly developed adoptive treatments of cancers. however,their therapeutic efficacy against solid tumors is limited. combining car-t or car-nk cells with chemotherapeutic drugs to treat solid tumor may be a promising strategy. we developed an epidermal growth factor- (egfr-) specific third-generation car. nk-92 cells were modified with the car by lentivirus infection. the specific killing ability of the car-modified nk-92 cells (car-nk-92) against renal cell carcinoma (rcc) cell lines was confirmed in vitro. the synergistic effects of cabozantinib and egfr-specific car-nk-92 cells were investigated in vitro and in vivo. our results showed that the car-nk-92 cells lyse rcc cells in an egfr-specific manner. treatment with cabozantinib could increase egfr and decrease pd-l1 membrane surface expression in rcc cells and enhance the killing ability of car-nk-92 cells against the rcc cells in vitro. furthermore,the car-nk-92 cells show synergistic therapeutic efficacy with cabozantinib against human rcc xenograft models. our results provided the basis for combination with chemotherapy as a novel strategy for enhancing the therapeutic efficacy of car-modified immune effector cells for solid tumors. © 2017 qing zhang et al.