Related Experiment Video
Updated: Jul 15, 2025
10:29
Generation of Human Chimeric Antigen Receptor Regulatory T Cells
Published on: January 3, 2025
1.4K
Conditional Control of Universal CAR T Cells by Cleavable OFF-Switch Adaptors
Michael Kvorjak1,2,3,4, Elisa Ruffo1,2,3,4, Yaniv Tivon5
1UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15232, United States.
ACS Synthetic Biology
|October 4, 2023
Summary
Engineered T cell therapies, or CAR T cells, can now be precisely controlled using novel OFF-switch adaptors. These adaptors enhance safety and allow for targeted treatment of multiple diseases with enhanced precision.
Area of Science:
- Immunology
- Biotechnology
- Oncology
Background:
- Engineered T cell therapies, including chimeric antigen receptor (CAR) T cells, offer revolutionary disease treatment potential.
- Current CAR T cell therapies face challenges with unpredictable behavior, toxicity, and pharmacokinetics.
- Conditional control mechanisms responsive to external stimuli are highly desirable for enhancing safety and programmability.
Purpose of the Study:
- To engineer OFF-switch adaptors for universal CAR T cells to enable conditional control of T cell activity.
- To enhance the safety and programmability of CAR T cell therapies.
- To investigate the potential for simultaneous targeting of multiple antigens using OFF-switch adaptors.
Main Methods:
- Development of novel OFF-switch adaptors for universal CAR T cells.
- Utilizing small molecules or light as stimuli to control CAR T cell activity.
- Testing adaptor combinations for orthogonal targeting and Boolean logic-based control.
Main Results:
- Engineered OFF-switch adaptors successfully controlled CAR T cell activation, target cell lysis, and transgene expression.
- OFF-switch adaptors demonstrated orthogonal conditional targeting of multiple antigens simultaneously.
- The system operated effectively following Boolean logic principles.
Conclusions:
- OFF-switch adaptors represent a significant advancement in the precision targeting of universal CAR T cells.
- This technology offers potential for enhanced safety and therapeutic efficacy in CAR T cell treatments.
- The developed system provides a robust platform for next-generation, controllable cellular immunotherapies.
