ArticleScience (New York, N.Y.)2022
Synthetic cytokine circuits that drive T cells into immune-excluded tumors.
Article in Science (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
151 citing papers in PubMed, 207 citations in OpenAlex.
- Synthetic Notch CD123 and CLL1 chimeric antigen receptor T-cells (CAR-T) target acute myeloid leukemia and reduce off-tumor effects associated with CLL1 CAR-T cells.Molecular biomedicine · 2026Article
- Genetically inducible coordinators of cytokine signaling pathways for interrogating T cell motility.bioRxiv : the preprint server for biology · 2026Article
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Receptor-defined targeting of a genomically unique melanoma-enriched noncanonical antigen.Signal transduction and targeted therapy · 2026Article
- 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
- Article
- The evolving role of cytokines for CAR-T cell manufacturing and beyond.Nature biomedical engineering · 2026Review
- Adoptive cell therapy in lung cancer: progress, challenges, and prospects.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Therapeutic modulation of the vitreoretinal fibrosis microenvironment in female mice using engineered macrophage-derived extracellular vesicles.Nature communications · 2026Article
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- CRISPR application in hematological disorders: from bench to bedside.Blood advances · 2026Review
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 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
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Nanomaterials targeting cancer-associated fibroblasts to overcome stromal barriers in cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- Advances in immune cell-based therapeutic agents for the treatment of inflammation-related diseases.Acta pharmaceutica Sinica. B · 2026Review
- Design principles of the cytotoxic CD8Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- Preventing trogocytosis by cathepsin B inhibition augments CAR T-cell function.Signal transduction and targeted therapy · 2026Article
91 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR) T cells are ineffective against solid tumors with immunosuppressive microenvironments. To overcome suppression, we engineered circuits in which tumor-specific synNotch receptors locally induce production of the cytokine IL-2. These circuits potently enhance CAR T cell infiltration and clearance of immune-excluded tumors, without systemic toxicity. The most effective IL-2 induction circuit acts in an autocrine and T cell receptor (TCR)- or CAR-independent manner, bypassing suppression mechanisms including consumption of IL-2 or inhibition of TCR signaling. These engineered cells establish a foothold in the target tumors, with synthetic Notch-induced IL-2 production enabling initiation of CAR-mediated T cell expansion and cell killing. Thus, it is possible to reconstitute synthetic T cell circuits that activate the outputs ultimately required for an antitumor response, but in a manner that evades key points of tumor suppression.
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What OpenQuestion holds
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.