iSynPro-Inducible Synthetic Promoters for Adoptive T-cell Therapies

Library of T-cell activation inducible synthetic promoters for repetitive and controlled gene expression and  screening-antigen-specific CARs and TCRs.

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Technology overview

Adoptive T-cell therapies including engineered TCR-based therapies and CAR T-cell therapies have emerged as powerful strategies to treat cancer. Enhancing the survival, proliferation and efficacy of the therapeutic T cells often requires the expression of specific genes, including cytokines, pro-proliferation genes, chimeric receptors, BiTEs and other soluble proteins. While constitutive expression of such genes can cause systemic toxicity, there is a need for tumor site specific expression after the therapeutic T cell encounters the tumor antigen.

Using a random ligation strategy, Dr. Michael Jensen and Dr. Jia Wei have created a library of synthetic promoters, “iSynPro(s)” that are inducible upon CAR T cell or TCR activation. In vitro studies have shown that reporter gene expression induced by iSynPro is significantly higher compared to inducible NFAT promoters. iSynPros not only display high level of sustained gene expression, but also show robust gene expression upon repeated induction. When coupled to reporter genes, iSynPros can screen novel CARs and TCRs for tumor antigen specificity and identify CARs with tonic signaling. iSynPros are versatile tools for adoptive T-cell therapies.

Applications

• Activated CAR T-cell specific gene expression
• CAR T-cell therapy for solid tumors
• Screening tool for antigen-specific CAR/TCR selection
• Screening tool to detect CARs with tonic signaling

Advantages

• High signal to noise ratio
• Synthetic promoters can be repetitively turned on and off
• Strong reporter gene expression compared to NFAT promoters

Market overview

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 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.

Availability

Non-exclusive license

Technology type

Gene expression tool

Screening tool

Technology status

Preclinical in vivo  

Patent status

National stage filings based on WO 2018/213332

Developers

Jia Wei, PhD
Michael Jensen, MD

Learn more

To learn more about this technology, please email Kamya Rajaram.