ArticleScientific reports2021
Tunable control of CAR T cell activity through tetracycline mediated disruption of protein-protein interaction.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- AI-GuidedJournal of the American Chemical Society · 2026Article
- Combining Small-Molecular Compounds With CAR T-Cell Therapy: Novel Strategies for Enhanced Cancer Immunotherapy.Cancer innovation · 2026Review
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- Advancing CAR-based cell therapies for solid tumours: challenges, therapeutic strategies, and perspectives.Molecular cancer · 2025Review
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- Multiplex engineering and multifunction T cells for precise and effective immunotherapies.Frontiers in immunology · 2025Review
- CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities.Brain sciences · 2024Review
- Regulation of CAR transgene expression to design semiautonomous CAR-T.Molecular therapy. Oncology · 2024Review
- Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.Experimental hematology & oncology · 2024Review
- Designer Small-Molecule Control System Based on Minocycline-Induced Disruption of Protein-Protein Interaction.ACS chemical biology · 2024Article
- Progress and Pitfalls of Chimeric Antigen Receptor T Cell Immunotherapy against T Cell Malignancies.Transplantation and cellular therapy · 2024Review
- Engineering enhanced chimeric antigen receptor-T cell therapy for solid tumors.Immuno-oncology technology · 2023Review
- Synthesizing a Smarter CAR T Cell: Advanced Engineering of T-cell Immunotherapies.Cancer immunology research · 2023Article
- Functional Validation of the RQR8 Suicide /Marker Gene in CD19 CAR-T Cells and CLL1CAR-T Cells.Annals of hematology · 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
- Review
- Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours.Nature reviews. Clinical oncology · 2023Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR) T cells are a promising form of cancer immunotherapy, although they are often associated with severe toxicities. Here, we present a split-CAR design incorporating separate antigen recognition and intracellular signaling domains. These exploit the binding between the tetracycline repressor protein and a small peptide sequence (TIP) to spontaneously assemble as a functional CAR. Addition of the FDA-approved, small molecule antibiotic minocycline, acts as an "off-switch" by displacing the signaling domain and down-tuning CAR T activity. Here we describe the optimization of this split-CAR approach to generate a CAR in which cytotoxicity, cytokine secretion and proliferation can be inhibited in a dose-dependent and reversible manner. Inhibition is effective during on-going CAR T cell activation and inhibits activation and tumor control in vivo. This work shows how optimization of split-CAR structure affects function and adds a novel design allowing easy CAR inhibition through an FDA-approved small molecule.
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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.