Title: Targeting PD-L1 in non-small cell lung cancer using CAR T cells.

Authors: Liu, Ming; Wang, Xu; Li, Wei; Yu, Xinfang; Flores-Villanueva, Pedro; Xu-Monette, Zijun Y; Li, Ling; Zhang, Mingzhi; Young, Ken H; Ma, Xiaodong; Li, Yong

Published In Oncogenesis, (2020 Aug 13)

Abstract: Antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the landscape of therapies for non-small cell lung carcinoma (NSCLC); however, the majority of patients do not respond to these agents. In addition, hyperprogressive disease (HPD) develops in a larger portion of NSCLC patients treated with PD-1/PD-L1 inhibitors than in patients treated with standard chemotherapy. The use of chimeric antigen receptor (CAR) T cells has been successful to treat blood cancers but not for solid tumors like NSCLC. In this work, we constructed CAR T cells that target PD-L1 and evaluated their efficacy in NSCLC with either high or low PD-L1 expression. PD-L1-CAR T cells exhibited antigen-specific activation, cytokine production, and cytotoxic activity against PD-L1high NSCLC cells and xenograft tumors. Furthermore, the addition of a subtherapeutic dose of local radiotherapy improved the efficacy of PD-L1-CAR T cells against PD-L1low NSCLC cells and tumors. Our findings indicate that PD-L1-CAR T cells represent a novel therapeutic strategy for patients with PD-L1-positive NSCLC, particularly for those who are susceptible to HPD.

PubMed ID: 32792499

MeSH Terms: No MeSH terms associated with this publication