Dual Promoter System for Adoptive T-cell Therapies
A novel construct housing a constitutive expression cassette and a T-cell activation inducible expression cassette
To enhance the efficacy of adoptive T-cell-based therapies, there is a need for controlled payload expression dictated by when and where a therapeutic T cell encounters a tumor antigen. T-cell activation inducible-promoter systems allow for such controlled payload expression. Currently, these systems utilize a two-component system, with a first vector for the CAR/TCR expression and a second vector for the inducible-payload expression. Key drawbacks of the two-component system include the need for utilizing separate drug-selectable markers for each construct and reduced efficiency of generating cells containing both constructs.
To overcome this limitation, Dr. Michael Jensen and Dr. Wei have designed a novel gene expression construct comprising two gene expression cassettes. A constitutive promoter drives one expression cassette and a patented synthetic promoter (iSynPro), which is inducible upon CAR T cell or TCR activation, drives the second expression cassette. Insulator sequences engineered into the construct isolate the dual promoter system from the surrounding chromosomal environment. Crosstalk between the two promoters is eliminated by insulator sequences and poly-A sequences housed between the two expression cassettes.
- Activated CAR T-cell-specific gene expression
- CAR T-cell therapy for solid tumors
- Screening tool for antigen specific CAR/TCR selection
- Screening tool for tonic signaling CAR detection
- Compatible with transposon-based or any plasmid-based vector designs
- Can be modified to work with viral vectors
- Use of a single drug selection marker for two gene expression cassettes
- Payload expression under iSynPro can be turned off by a drug inhibitor
- iSynPro can be repetitively turned on and off
The global T-cell therapy market was worth USD $2.4 billion in 2018 and is expected to grow at a CAGR of 15.4% from 2018 to 2027. The value of the CAR T-cell therapy market is expected to reach USD $2.9 billion by 2023, growing at a CAGR of 44.1% from 2018 to 2023.
Gene expression tool
Preclinical in vivo
Jia Wei, PhD
Michael Jensen, MD
To learn more about this technology, please email Kamya Rajaram.