ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Ligand-Induced Degradation of a CAR Permits Reversible Remote Control of CAR T Cell Activity In Vitro and In Vivo.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 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 58 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Precise control of switchable chimeric antigen receptor T cells allows enhanced safety and less T cell exhaustion.Journal of translational medicine · 2026Article
- Development of CAR NK Cell Lines Selectively Targeting Cancer Cells Expressing Membrane Hsp70.MedComm · 2026Article
- Different Immune Cells Modified With Chimeric Antigen Receptors Are Being Applied to Ovarian Cancer: Which Is the Most Effective?Cancer medicine · 2026Review
- Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies.Frontiers in immunology · 2026Review
- Targeting the synovial engine: next-generation engineered immune cells to eradicate pathogenic FLS in rheumatoid arthritis, with safety-first, selective designs.Frontiers in immunology · 2026Review
- Advancements and expanding applications of CAR-T cell therapy.Frontiers in immunology · 2026Review
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- RNA-stabilized coat proteins for sensitive and simultaneous imaging of distinct single mRNAs in live cells.Nature methods · 2026Article
- Chemically-inducible CRISPR/Cas9 circuits for ultra-high dynamic range gene perturbation.Nature communications · 2025Article
- Precise Control of Switchable Chimeric Antigen Receptor T Cells Allows Enhanced Safety and Less T Cell Exhaustion.bioRxiv : the preprint server for biology · 2025Article
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- Current status of chimeric antigen receptor T cell therapy and its exhaustion mechanism.Immunotherapy · 2025Review
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- Chimeric antigen receptor T-cell therapy in patients with malignant glioma-From neuroimmunology to clinical trial design considerations.Neuro-oncology · 2025Review
- Degradation bottlenecks and resource competition in transiently and stably engineered mammalian cells.Nature communications · 2025Article
- Advances in chimeric antigen receptor-natural killer cell therapy: from mechanisms and preclinical studies to clinical application.Frontiers in oncology · 2025Review
- Myeloid cells meet CD8Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Evolving strategies for addressing CAR T-cell toxicities.Cancer metastasis reviews · 2024Review
- Advancing Chimeric Antigen Receptor T-Cell Therapy for Acute Myeloid Leukemia: Current Limitations and Emerging Strategies.Pharmaceuticals (Basel, Switzerland) · 2024Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR)-modified T cells are endowed with novel antigen specificity and are most often administered to patients without an engineered mechanism to control the CAR T cells once infused. "Suicide switches" such as the small molecule-controlled, inducible caspase-9 (iCas9) system afford the ability to selectively eliminate engineered T cells; however, these approaches are designed for all-or-none, irreversible termination of an ongoing immune response. In order to permit reversible and adjustable modulation, we have created a CAR that is capable of on-demand downregulation by fusing the CAR to a previously developed ligand-induced degradation (LID) domain. Addition of a small molecule ligand triggers exposure of a cryptic degron within the LID domain, resulting in proteasomal degradation of the CAR-LID fusion protein and loss of CAR on the surface of T cells. This fusion construct allowed for reversible and "tunable" inhibition of CAR T cell activity in vitro. Delivery of the triggering molecule in CAR-LID-treated tumor-bearing mice temporarily reduced CAR activity through modulation of CAR surface expression. The ability to more flexibly modulate CAR T cell expression through a small molecule provides a platform for controlling possible adverse side effects, as well as preclinical investigations of CAR T cell biology.
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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.