1. Generation of regulable EGFRvIII targeted chimeric antigen receptor T cells for adoptive cell therapy of glioblastoma
- Author
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Yu-Long Fu, Xiu-Ling Li, Yan Zheng, Albert J. Wong, Bingyong Zhang, Tian-Fang Li, Ning Gao, Puja Gupta, and Shuang-Yin Han
- Subjects
0301 basic medicine ,Lysis ,Time Factors ,T cell ,T-Lymphocytes ,Cell ,Biophysics ,Dose-Response Relationship, Immunologic ,Lymphocyte Activation ,Biochemistry ,Immunotherapy, Adoptive ,Cell therapy ,Small Molecule Libraries ,03 medical and health sciences ,Jurkat Cells ,Antigen ,medicine ,Humans ,Epidermal growth factor receptor ,Molecular Biology ,Receptors, Chimeric Antigen ,biology ,Cell Biology ,Small molecule ,Chimeric antigen receptor ,ErbB Receptors ,030104 developmental biology ,medicine.anatomical_structure ,HEK293 Cells ,Cancer research ,biology.protein ,Glioblastoma - Abstract
Adoptive immunotherapy using chimeric antigen receptors-modified T cells (CAR-T) is a promising approach for cancer treatment. However, CARs currently applied in the clinics cannot be effectively regulated and the safety of CAR-T cell therapies remains a major concern. To improve the safety of CAR-T cells, we designed a synthetic splitting CAR (ssCAR) that can regulate T cell functions exogenously. Epidermal growth factor receptor variant III (EGFRvIII) was used as a molecular target for ssCAR. Our results indicate that both EGFRvIII and small molecule are needed for the activation of the ssCAR-T cells. AP21967 dose-dependently increased the expression of T cell activation, production of cytokines and extent of cell lysis. In conclusion, the gene switch designed in this study allows for temporal and spatial control over engineered T cells in a dose-and time-dependent manner by AP21967. Our work demonstrates the feasibility and improved safety profile of this novel treatment approach.
- Published
- 2018