Bi-specific ligand-controlled chimeric antigen receptor T-cell therapy for non-small cell lung cancer

Wenqi Chu; Yixiong Zhou; Qi Tang; Min Wang; Yongjia Ji; Jingjing Yan; Dan Yin; Shuye Zhang; Hongzhou Lu; Jiayin Shen

doi:10.5582/bst.2018.01048

Original Articles

Bi-specific ligand-controlled chimeric antigen receptor T-cell therapy for non-small cell lung cancer

Wenqi Chu, Yixiong Zhou, Qi Tang, Min Wang, Yongjia Ji, Jingjing Yan, Dan Yin, Shuye Zhang, Hongzhou Lu, Jiayin Shen

Author information

Wenqi Chu
Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University
Yixiong Zhou
Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine
Qi Tang
Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University
Min Wang
Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University
Yongjia Ji
Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University
Jingjing Yan
Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University
Dan Yin
Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University
Shuye Zhang
Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University
Hongzhou Lu
Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University
Department of Infectious Diseases, Huashan Hospital Affiliated to Fudan University
Jiayin Shen
Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University

Keywords: Non-small cell lung cancer, chimeric antigen receptor T cell, folate receptor, folate-FITC

JOURNAL FREE ACCESS

2018 Volume 12 Issue 3 Pages 298-308

DOI https://doi.org/10.5582/bst.2018.01048

Browse “Advance online publication” version

Details

Abstract

Our goal is to develop a switch-controlled approach to enable better control of reactivity and safety of chimeric antigen receptor (CAR)-T therapy for non-small-cell lung cancer (NSCLC). Lentiviral transduction was performed to generate anti-FITC CAR-T cells and target cells stably expressing either isoform of the folate receptor. Colorimetric-based cytotoxic assay, enzyme-linked immunosorbent assay, and multiparametric flow cytometry analysis were used to evaluate the specificity and activity of CAR-T cells in vitro. Human primary T cells stably expressing the fully human anti-FITC CAR were generated. Anti-FITC CAR-T cells displayed antigen-specific and folate-FTIC dependent reactivity against engineered A549-FRα and THP-1-FRβ. The selective activation and proliferation of anti-FITC CAR-T cells in vitro stringently relied on the co-existence of folate-FITC and FR- expressing target cells and was dose-titratable with the folate-FITC switch. The excellent in vitro efficacy and specificity of an adaptor-controlled CAR-T therapy to target both tumor cells and tumor-associated macrophages in NSCLCs were validated.

Corresponding author

Register with J-STAGE for free!