Use of AXL-specific CAR T cells to treat non-small-cell lung cancer

Abstract The application of Chimeric antigen receptor (CAR) T cells in solid tumors is hindered by lack of tumor specific targets and inefficient T cell infiltration in tumor. It has been postulated that AXL may be an ideal immunotherapy target for non-small-cell lung cancer (NSCLC). Here, we screened 208 non-tumor samples from 22 types of human organs or tissues and 90 tumor samples from NSCLC patients by immunohistochemistry or Western Blotting and identified that AXL was rarely expressed in normal tissues but highly expressed in 69% NSCLC samples, suggesting AXL is an ideal target for CAR T cell therapy for lung cancer. We generated low-, mediate-, high-affinity AXL-CARs and evaluated their killing effect on NSCLC. Our data demonstrated antitumor effects of AXL-CAR T cell therapy for various NSCLC models both in vitro and in vivo. AXL-CAR T cells alone exerted strong antitumor effect in subcutaneous lung cancer cell derived xenograft (CDX), pulmonary metastases CDX, and intraperitoneal CDX models. Intraperitoneal delivery of CAR T cells resulted in superior tumor killing effects compared with systemic infusions for the intraperitoneal CDX tumor models. AXL-CAR T combined with microwave ablation (MWA) or EGFR-TKI resulted in enhanced killing effect and CAR-T cell infiltration in vivo. Together, our current study suggests that systemic or regional infusion of AXL-CAR T cell alone or combination with other therapies might have potential translatable value for the treatment of NSCLC in clinical situation.