A Reversible Chemogenetic Switch for Chimeric Antigen Receptor TCells. Academic Article uri icon

abstract

  • As a revolutionary cancer treatment, the chimeric antigen receptor (CAR) T cell therapy suffers from complications such as cytokine release syndromes and T cell exhaustion. Their mitigation desires controllable activation of CAR-T cells that is achievable through regulatory display of CARs. By embedding the hepatitis C virus NS3 protease (HCV-NS3) between the single-chain variable fragment (scFv) and the hinge domain, we showed that the display of anti-CD19 scFv on CAR-T cells was positively correlated to the presence of a clinical HCV-NS3 inhibitor asunaprevir (ASV). This novel CAR design that allows the display of anti-CD19 scFv in the presence of ASV and its removal in the absence of ASV creates a practically reversible chemical switch. We demonstrated that the intact CAR on T cells can be repeatedly turned on and off by controlling the presence of ASV in a dose dependent manner both in vitro and in vivo, which enables delicate modulation of CAR-T activation during cancer treatment.

published proceedings

  • Angew Chem Int Ed Engl

altmetric score

  • 12.4

author list (cited authors)

  • Cao, W., Geng, Z. Z., Wang, N. a., Pan, Q., Guo, S., Xu, S., Zhou, J., & Liu, W. R.

citation count

  • 6

complete list of authors

  • Cao, Wenyue||Geng, Zhi Zachary||Wang, Na||Pan, Quan||Guo, Shaodong||Xu, Shiqing||Zhou, Jianfeng||Liu, Wenshe Ray

publication date

  • January 2022

publisher