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A Reversible Chemogenetic Switch for Chimeric Antigen Receptor T Cells
Wenyue Cao1,2, Zhi Zachary Geng2, Na Wang1
1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Angewandte Chemie (International Ed. in English)
|November 16, 2021
Summary
This study introduces a novel chimeric antigen receptor (CAR) T cell therapy switch. The CAR T cell therapy
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment.
- CAR T cell therapy faces challenges including cytokine release syndrome and T cell exhaustion.
- Controllable CAR T cell activation is crucial for mitigating these side effects.
Purpose of the Study:
- To develop a controllable CAR T cell activation system.
- To create a reversible chemical switch for CAR T cell display.
- To enable precise modulation of CAR T cell activity during cancer treatment.
Main Methods:
- Engineered CAR T cells by embedding hepatitis C virus NS3 protease (HCV-NS3) between the scFv and hinge domain.
- Utilized the HCV-NS3 inhibitor asunaprevir (ASV) to control CAR T cell display.
- Assessed CAR T cell activation in vitro and in vivo through dose-dependent ASV presence.
Main Results:
- CAR T cell display of anti-CD19 scFv was positively correlated with ASV presence.
- The novel CAR design functions as a reversible chemical switch, controlled by ASV.
- CAR T cell activity was repeatedly turned on and off by modulating ASV levels.
Conclusions:
- A novel, reversible CAR T cell activation system was successfully developed.
- This system allows for fine-tuning of CAR T cell activity, offering improved safety and efficacy.
- The ASV-controlled CAR T cell therapy holds potential for enhanced cancer treatment strategies.
