ArticlePloS one2018
Feasibility of controlling CD38-CAR T cell activity with a Tet-on inducible CAR design.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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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.
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Who cites it
52 citing papers in PubMed, 72 citations in OpenAlex.
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Genetic Code Expanded T Cell for Controllable Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multifunctional CD38 in the pathogenesis and treatment of B-cell lymphomas.American journal of blood research · 2026Review
- Engineering of induced pluripotent stem cells for the efficient development of non-alloreactive, hypoimmunogenic CD8αβ CAR-T cells.Frontiers in immunology · 2026Article
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- Engineering resilient CAR T cells for immunosuppressive environment.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- CAR-NK cell therapy: promise and challenges in solid tumors.Frontiers in immunology · 2025Review
- Myeloid cells meet CD8Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Regulation of CAR transgene expression to design semiautonomous CAR-T.Molecular therapy. Oncology · 2024Review
- Design and mathematical analysis of activating transcriptional amplifiers that enable modular temporal control in synthetic juxtacrine circuits.Synthetic and systems biotechnology · 2023Article
- Challenges and new technologies in adoptive cell therapy.Journal of hematology & oncology · 2023Review
- Lentiviral vectors for inducible, transactivator-free advanced therapy medicinal products: Application to CAR-T cells.Molecular therapy. Nucleic acids · 2023Article
- Strategies for Reducing Toxicity and Enhancing Efficacy of Chimeric Antigen Receptor T Cell Therapy in Hematological Malignancies.International journal of molecular sciences · 2023Review
- Single-Cell Discovery and Multiomic Characterization of Therapeutic Targets in Multiple Myeloma.Cancer research · 2023Article
- Harnessing novel strategies and cell types to overcome immune tolerance during adoptive cell therapy in cancer.Journal for immunotherapy of cancer · 2023Review
- Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility.Journal of translational medicine · 2023Review
- Recent progress of gene circuit designs in immune cell therapies.Cell systems · 2022Review
- Engineering T-cells with chimeric antigen receptors to combat hematological cancers: an update on clinical trials.Cancer immunology, immunotherapy : CII · 2022Review
- Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies.Stem cell research & therapy · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent clinical advances with chimeric antigen receptor (CAR) T cells have led to the accelerated clinical approval of CD19-CARs to treat acute lymphoblastic leukemia. The CAR T cell therapy is nevertheless associated with toxicities, especially if the CARs are not entirely tumor-specific. Therefore, strategies for controlling the CAR T cell activity are required to improve their safety profile. Here, by using the multiple myeloma (MM)-associated CD38 molecule as target molecule, we tested the feasibility and utility of a doxycycline (DOX) inducible Tet-on CD38-CAR design to control the off-target toxicities of CAR T cells. Using CARs with high affinity to CD38, we demonstrate that this strategy allows the proper induction of CD38-CARs and CAR-mediated T cell cytotoxicity in a DOX-dose dependent manner. Especially when the DOX dose was limited to 10ng/ml, its removal resulted in a relatively rapid decay of CAR- related off-tumor effects within 24 hours, indicating the active controllability of undesired CAR activity. This Tet-on CAR design also allowed us to induce the maximal anti-MM cytotoxic activity of affinity-optimized CD38-CAR T cells, which already display a low toxicity profile, hereby adding a second level of safety to these cells. Collectively, these results indicate the possibility to utilize this DOX inducible CAR-design to actively regulate the CAR-mediated activities of therapeutic T cells. We therefore conclude that the Tet-on system may be more advantageous above suicide-genes to control the potential toxicities of CAR T cells without the need to destroy them permanently.
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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.