LunX-CAR T Cells as a Targeted Therapy for Non-Small Cell Lung Cancer

Abstract

Non-small cell lung cancer (NSCLC) carries a high mortality, and efficacious therapy is lacking. Therapy using chimeric antigen receptor (CAR) T cells has been used efficaciously against hematologic malignancies, but the curative effect against solid tumors is not satisfactory. A lack of antigen targets is one of the main reasons for this limited efficacy. Previously, we showed that lung-specific X (LUNX; also known as BPIFA1, PLUNC, and SPLUNC1) is overexpressed in lung cancer cells. Here, we constructed a CAR-T-cell-based strategy to target LunX (CAR ^LunX T cells). CAR T cells were developed so that, upon specific recognition of LunX, they secreted cytokines and killed LunX-positive NSCLC cells. In vitro, CAR ^LunX T cells displayed enhanced toxicity toward NSCLC lines and production of cytokines and showed specific LunX-dependent recognition of NSCLC cells. Adoptive transfer of CAR ^LunX T cells induced regression of established metastatic lung cancer xenografts and prolonged survival. CAR ^LunX T cells could infiltrate into the tumor. Also, we constructed a patient-derived xenograft model of lung cancer. After therapy with CAR ^LunX T cells, tumor growth was suppressed, and survival was prolonged significantly. Together, our findings offer preclinical evidence of the immunotherapeutic targeting of LunX as a strategy to treat NSCLC.

Graphical Abstract

Abstract

CAR-T cell therapy has been used for many kinds of cancers, but the specific target antigen for non-small cell lung cancer (NSCLC) is rare. Hu et al. report the CAR ^LunX-T cell therapy for NSCLC. By treatment with CAR ^LunX-T cells, the tumor growth was inhibited significantly in the mouse model.