BioScience Trends. 2018;12(3):298-308. (DOI: 10.5582/bst.2018.01048)

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

Chu WQ, Zhou YX, Tang Q, Wang M, Ji YJ, Yan JJ, Yin D, Zhang SY, Lu HZ, Shen JY

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 FRexpressing 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.

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