Generation of regulable EGFRvIII targeted chimeric antigen receptor T cells for adoptive cell therapy of glioblastoma

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...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2018-12, Vol.507 (1-4), p.59-66
Main Authors: Zheng, Yan, Gao, Ning, Fu, Yu-Long, Zhang, Bing-Yong, Li, Xiu-Ling, Gupta, Puja, Wong, Albert J., Li, Tian-Fang, Han, Shuang-Yin
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Chimeric antigen receptor
Glioblastoma
GLIOMAS
IMMUNOTHERAPY
LYMPHOKINES
RECEPTORS
Regulation
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2018.10.151