caTCF1 - An Engineered Transcription Factor to Supplement CAR T-cell Therapy

An engineered, constitutively active TCF1 to promote expression of memory-associated traits in CAR T cells

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Technology overview

Memory T cells feature high proliferative potential and persistence, two characteristics that are advantageous in adoptive T-cell products. Indeed, CAR T cells generated from central memory cells provide superior antitumor activity compared to CAR T cells generated from other T-cell subsets. Current approaches to regulate T-cell differentiation have focused on manipulating cell culture conditions and using transcription factors to differentiate T cells away from the exhausted condition. TCF1 is a transcription factor that plays a key role in the differentiation of memory T cells and can sustain T cell activity even after prolonged antigen exposure. Notably, analysis of CAR T cells from CLL patients with better clinical outcomes showed elevated TCF1 expression levels.

Dr. Jensen and colleagues have developed a novel approach to promote memory associated traits in CAR T cells. They have engineered a constitutively active version of TCF1 (caTCF1) by fusing TCF1 with the trans-activating domain of β catenin. caTCF1 activated reporter gene expression independent of β catenin in vitro, and CD8 T cells expressing caTCF1 demonstrated higher expression of memory associated markers.

Applications

• Promotion of memory T-cell differentiation and/or delay of terminal effector differentiation
• CAR T-cell retention of memory-associated traits

Advantages

• β catenin association independent activation of TCF1 driven transcription
• An engineered transcription factor that co-opts an endogenous transcriptional program
• Small DNA footprint of ~1.1 kilobases

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 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.

Availability

Non-exclusive license

Technology type

Cell therapy

Engineered transcription factor

Technology status

Preclinical in vivo

Patent status

Patent pending

Developers

Michael Jensen, MD
Christopher Saxby

Learn more

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