ArticleScience (New York, N.Y.)2021
T cell circuits that sense antigen density with an ultrasensitive threshold.
Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 174 citations in OpenAlex.
- Beyond Oncology: Exploring the Expanding Role of CAR T Cell Therapy in Autoimmune and Infectious Diseases-A Systematic Review.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Recent advances in molecular mechanisms to improve the efficacy of CAR-T cell therapy for viral diseases, cancer, and autoimmune diseases.Stem cell research & therapy · 2026Review
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 2026Review
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Manufacturing synthetic viscoelastic antigen-presenting cells for immunotherapy.Nature protocols · 2026Review
- Progress in the development of cytokine armoured CAR T cells.Nature reviews. Immunology · 2026Review
- Ultrasound priming gated by solid tumor hallmarks to guide CAR-T therapy.Science advances · 2026Article
- From CRISPR functional genomics to synthetic interventions: engineering antiviral strategies.Journal of virology · 2026Review
- Subcellular transcriptome sequencing with single cell APEX-seq identifies regulators of cell-cell interactions.bioRxiv : the preprint server for biology · 2026Article
- A framework integrating multiscale in silico modeling and experimental data predicts CAR-NK cell cytotoxicity across target cell types.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Engineering single-vector logic-gated CAR T cells with transgene sizes beyond current limitations.Journal for immunotherapy of cancer · 2026Article
- Enhancing the transduction efficiency of lentiviral vectors in CAR-T cell therapy through an optimization workflow.Frontiers in medicine · 2026Article
- T cell exhaustion landscapes and therapeutic modulation in cancer immunity.Frontiers in cell and developmental biology · 2026Review
- Monoclonal Antibodies and Derivatives: Therapeutic Tools for Cancer.Oncology research · 2026Review
- Regulation of T cell exhaustion and stemness: molecular mechanisms and implications for cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Engineering CAR-T cells for solid tumors: overcoming antigenic, trafficking, and microenvironmental barriers.Frontiers in immunology · 2026Review
- Directed evolution of LaccID for cell surface proximity labeling and electron microscopy.Nature chemical biology · 2025Article
- Review
- Multivalency Enables Signal Processing at Single Protein Level.Journal of the American Chemical Society · 2025Article
- Chimeric antigen receptor modified hematopoietic stem cells (CAR-HSCs) arm all immune forces for anti-tumor in mice.Experimental hematology & oncology · 2025Article
51 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Overexpressed tumor-associated antigens [for example, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2)] are attractive targets for therapeutic T cells, but toxic "off-tumor" cross-reaction with normal tissues that express low levels of target antigen can occur with chimeric antigen receptor (CAR)-T cells. Inspired by natural ultrasensitive response circuits, we engineered a two-step positive-feedback circuit that allows human cytotoxic T cells to discriminate targets on the basis of a sigmoidal antigen-density threshold. In this circuit, a low-affinity synthetic Notch receptor for HER2 controls the expression of a high-affinity CAR for HER2. Increasing HER2 density thus has cooperative effects on T cells-it increases both CAR expression and activation-leading to a sigmoidal response. T cells with this circuit show sharp discrimination between target cells expressing normal amounts of HER2 and cancer cells expressing 100 times as much HER2, both in vitro and in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.