ArticleCancer immunology research2021
CRASH-IT Switch Enables Reversible and Dose-Dependent Control of TCR and CAR T-cell Function.
Article in Cancer immunology research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 30 citations in OpenAlex.
- Adoptive cell therapies in thoracic malignancies: a comprehensive review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.Journal of hematology & oncology · 2025Review
- Current developments in T-cell receptor therapy for acute myeloid leukemia.Blood advances · 2025Review
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- SynNotch CAR-T cell, when synthetic biology and immunology meet again.Frontiers in immunology · 2025Review
- Tracing the development of CAR-T cell design: from concept to next-generation platforms.Frontiers in immunology · 2025Review
- Inhibitory CARs fail to protect from immediate T cell cytotoxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Enhancing the safety of CAR-T cell therapy: Synthetic genetic switch for spatiotemporal control.Science advances · 2024Review
- ReCARving the future: bridging CAR T-cell therapy gaps with synthetic biology, engineering, and economic insights.Frontiers in immunology · 2024Review
- Application of novel CAR technologies to improve treatment of autoimmune disease.Frontiers in immunology · 2024Review
- Building safety into CAR-T therapy.Human vaccines & immunotherapeutics · 2023Review
- Synthesizing a Smarter CAR T Cell: Advanced Engineering of T-cell Immunotherapies.Cancer immunology research · 2023Article
- Regulation of CD19 CAR-T cell activation based on an engineered downstream transcription factor.Molecular therapy oncolytics · 2023Article
- Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility.Journal of translational medicine · 2023Review
- Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours.Nature reviews. Clinical oncology · 2023Review
- Design and engineering of genetically encoded protein biosensors for small molecules.Current opinion in biotechnology · 2022Review
- Resistance against anti-CD19 and anti-BCMA CAR T cells: Recent advances and coping strategies.Translational oncology · 2022Review
- To go or not to go? Biological logic gating engineered T cells.Journal for immunotherapy of cancer · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adoptive transfer of genetically modified or donor-derived T cells can efficiently eradicate human tumors but is also frequently associated with major toxicity. There are several switches that can be used to kill the infused cell pool in the case of major toxicity, but the irreversible nature of these suicide switches means that the therapeutic effect is lost when they are used. To address this issue, we engineered a small-molecule responsive genetic safety switch that in the absence of drug robustly blocked cytotoxicity and cytokine expression of primary human T cells. Upon administration of drug, T-cell functions were restored in a reversible and titratable manner. We showed that this T-cell switch was universal, as it could be combined with endogenous or transduced T-cell receptors (TCR), as well as chimeric antigen receptors. The modular nature of the Chemically Regulated - SH2-delivered Inhibitory Tail (CRASH-IT) switch concept, in which inhibitory domains are brought to activating immune receptors in a controlled manner, makes it a versatile platform to regulate the activity of cell products that signal through immunoreceptor tyrosine-based activation motif (ITAM)-containing receptors.
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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.