ArticleNature chemical biology2026
IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers.
Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mast cell extracellular granules are bioactive condensates assembled by heparin and polyamine.Nature chemical biology · 2026Article
- CAR-T cell signaling dynamics, rational design principles and artificial intelligence for next-generation chimeric antigen receptors.Frontiers in immunology · 2026Review
- Mast cell extracellular granules are bioactive condensates driven by heparin and polyamine.bioRxiv : the preprint server for biology · 2025Article
- CSF1R-CAR T cells induce CSF1R signaling and can promote target cell proliferation.Science signaling · 2025Article
- Tailoring CAR surface density and dynamics to improve CAR-T cell therapy.Journal for immunotherapy of cancer · 2025Review
- CAR-T Entering a New "Phase": Improving CAR-T Function by Harnessing Phase Separation.Cancer research · 2025Article
- Interplay between membranes and biomolecular condensates in the regulation of membrane-associated cellular processes.Experimental & molecular medicine · 2024Review
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9 authors.
Funding
Abstract
Chimeric antigen receptor (CAR)-T cell therapies have shown remarkable efficacies for 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 FUS IDR CAR-T induced improved antitumor effects in both blood cancer and solid tumor models. No spontaneous activation in the absence of antigen was observed. Together, our work demonstrates IDRs as a new toolset for improving CAR-T function through inducing biomolecular condensation.
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