ArticleNature biotechnology2020
A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy.
Article in Nature biotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers.
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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
76 citing papers in PubMed, 150 citations in OpenAlex.
- Drug-controlled CAR T cells through the regulation of cell-cell interactions.Nature chemical biology · 2026Article
- Reversible control of CAR T cells through PROTAC compound targeting bromodomain mutant.Molecular therapy. Oncology · 2026Article
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 2026Review
- AI-GuidedJournal of the American Chemical Society · 2026Article
- Computational design of synthetic receptors with programmable signalling activity for enhanced cancer T cell therapy.Nature biomedical engineering · 2026Article
- Review
- Identification of affinity-optimized peptide binders of a viral protease for chemical genetic applications.Bioorganic & medicinal chemistry letters · 2026Article
- MGTbind: a comprehensive database of molecular glue ternary interactome.Nucleic acids research · 2026Article
- Generation and Characterization of CAR-T Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- CSF1R-CAR T cells induce CSF1R signaling and can promote target cell proliferation.Science signaling · 2025Article
- Engineering TME-gated inducible CAR-T cell therapy for solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- Ligand-induced assembly of antibody variable fragments for the chemical regulation of biological processes.Cell chemical biology · 2025Article
- Identification of clinically relevant T cell receptors for personalized T cell therapy using combinatorial algorithms.Nature biotechnology · 2025Article
- Article
- Bioengineered therapeutic systems for improving antitumor immunity.National science review · 2025Review
- Advancing Cancer Immunotherapy Using Lipid Nanoparticle-Based Approaches.International journal of nanomedicine · 2025Review
- Stem Loop Mediated Transgene Modulation in Human T Cells.ACS synthetic biology · 2024Article
- Dual ON/OFF-switch chimeric antigen receptor controlled by two clinically approved drugs.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Approaches to increase the activity of chimeric antigen receptor (CAR)-T cells against solid tumors may also increase the risk of toxicity and other side effects. To improve the safety of CAR-T-cell therapy, we computationally designed a chemically disruptable heterodimer (CDH) based on the binding of two human proteins. The CDH self-assembles, can be disrupted by a small-molecule drug and has a high-affinity protein interface with minimal amino acid deviation from wild-type human proteins. We incorporated the CDH into a synthetic heterodimeric CAR, called STOP-CAR, that has an antigen-recognition chain and a CD3ζ- and CD28-containing endodomain signaling chain. We tested STOP-CAR-T cells specific for two antigens in vitro and in vivo and found similar antitumor activity compared to second-generation (2G) CAR-T cells. Timed administration of the small-molecule drug dynamically inactivated the activity of STOP-CAR-T cells. Our work highlights the potential for structure-based design to add controllable elements to synthetic cellular therapies.
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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.