XU Chenqi lab contributes a preview article discussing a new screening system for T cell therapies
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Time: 2020-05-12
T cell therapies have achieved great success in treating hematologic malignancies but facing difficulties in treating solid tumor. XU Chenqi was invited by Cancer Cell to contribute a preview discussing a CRISPR-based platform for developing T cell therapies, which allows discovery of constructs promoting T cell anti-tumor activity.
In a recent Cell paper by Marson and colleagues, the researchers developed a method for pooled knockin screening of large DNA sequences at the endogenous TCRa constant (TRAC) locus. They designed a 36-member library of barcoded templates, which enables the quantification of on-target integration of each construct. They further developed pooled knockin sequencing (PoKI-seq), combing single-cell transcriptome analysis and pooled knockin screening to measure cell abundance and cell states ex vivo and in vivo. Using this innovative technology, they found that a novel chimeric TGF-bR2-41BB receptor, which convert suppressive TGFb signaling to stimulatory 41BB signaling, enhanced T cell fitness and thus promoted solid tumor clearance. This pooled knockin platform will accelerate discovery of new constructs for T cell therapies.
Contact: cqxu@sibcb.ac.cn
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