A Reversible Chemogenetic Switch for Chimeric Antigen Receptor T Cells** Academic Article uri icon

abstract

  • AbstractAs 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 CART cells that is achievable through regulatory display of CARs. By embedding the hepatitis C virus NS3 protease (HCVNS3) between the singlechain variable fragment (scFv) and the hinge domain, we showed that the display of antiCD19 scFv on CART cells was positively correlated to the presence of a clinical HCVNS3 inhibitor asunaprevir (ASV). This novel CAR design that allows the display of antiCD19 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 CART activation during cancer treatment.

published proceedings

  • Angewandte Chemie

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

  • 0

complete list of authors

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

publication date

  • March 2022

publisher