Improving the anti-tumor efficacy of CAR-T through biomolecular condensation (中文)

Chimeric antigen receptor (CAR)-T cell therapies showed remarkable efficacies in treating otherwise intractable cancers. However, current clinically approved CAR-T therapies are limited by low antigen sensitivity, impeding their efficacy against cancers with low antigen expression. Here, to address this issue, we engineered CARs targeting CD19, CD22 and HER2 by including intrinsically disordered regions (IDRs) that promote signaling condensation. We discovered that the CAR fused with an IDR from FUS, EWS or TAF15 promoted the formation of CAR-T conjugation with cancer targets, the mechanical strength of CAR-T synapses and membrane-proximal signaling, which led to an increased release of cytotoxic factors and a higher killing activity toward low-antigen-expressing cancer cells in vitro. Moreover, the IDR CAR-T displayed improved antitumor effects in both blood cancer and solid tumor models. No elevated tonic signaling was observed. Together, our work demonstrates IDRs as a new toolset for improving CAR-T function through inducing biomolecular condensation.

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This webinar will be in Chinese. 此次线上研讨会为中文讲座

Local Time: 9:00 PM (China Standart Time) 北京时间 9:00 PM

Join via #Tencent meeting：423-135-630