ArticleJournal of hematology & oncology2021
Dasatinib enhances anti-leukemia efficacy of chimeric antigen receptor T cells by inhibiting cell differentiation and exhaustion.
Article in Journal of hematology & oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 70 citations in OpenAlex.
- BTK Inhibitor Synergizes With CD19-Targeted Chimeric Antigen Receptor-T Cells in Patients With Relapsed or Refractory B-Cell Lymphoma: An Open-Label Pragmatic Clinical Trial.Cancer medicine · 2025Trial
- Improved outcomes with TKI maintenance after brexucabtagene autoleucel in Philadelphia chromosome ALL.Blood advances · 2026Article
- Dasatinib reversibly disrupts T cell motility and activation in lymph nodes.Science advances · 2026Article
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Combining Small-Molecular Compounds With CAR T-Cell Therapy: Novel Strategies for Enhanced Cancer Immunotherapy.Cancer innovation · 2026Review
- Th17-driven CD8Cell death & disease · 2026Article
- CAR-T cell exhaustion in B cell lymphoma: Current status, mechanisms, and potential solutions.Molecular therapy. Oncology · 2026Review
- Targeting CAR-T cell exhaustion in non-Hodgkin lymphoma: mechanistic insights and emerging clinical strategies.Frontiers in immunology · 2026Review
- International consensus guidelines for the conduct and reporting of CAR T-cell clinical trials in AML.Blood advances · 2025Article
- Tempered signal strength via low-dose MEK inhibition optimizes therapeutic performance of engineered T cells.Journal for immunotherapy of cancer · 2025Article
- Immunophenotype of CAR T cells and apheresis products predicts response in CD22 CAR T cell trial for B cell acute lymphoblastic leukemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Overcoming B-ALL Resistance to Targeted and Immune Therapies by Rational Combination Strategies.Blood cancer discovery · 2025Review
- Presetting CAR-T cells during ex vivo biomanufacturing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Selective JAK2 pathway inhibition enhances anti-leukemic functionality in CD19 CAR-T cells.Cancer immunology, immunotherapy : CII · 2025Article
- Advances in the combination of CAR-T therapy with small-molecule reagents for hematologic malignancies.Frontiers in immunology · 2025Review
- 2B4 co-stimulation and dasatinib modulation enhance anti-CD19 CAR-NK-92 cell cytotoxicity.Frontiers in immunology · 2025Article
- Preclinical Evaluation of AZD6422, an Armored Chimeric Antigen Receptor T Cell Targeting CLDN18.2 in Gastric, Pancreatic, and Esophageal Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB.Signal transduction and targeted therapy · 2024Article
- BRD4 inhibitor reduces exhaustion and blocks terminal differentiation in CAR-T cells by modulating BATF and EGR1.Biomarker research · 2024Article
- Combination Therapy With Asciminib and Ponatinib as a Bridge to Brexucabtagene Autoleucel and Maintenance in a Patient With Relapsed Refractory Philadelphia Positive B-Cell Acute Lymphoblastic Leukemia.Journal of medical cases · 2024Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Relapses of CD19-expressing leukemia in patients who achieved initial remission after CART cell treatment have been reported to correlate with poor CART cells persistence. Sustained tonic signaling or strong activation drives CART cell differentiation and exhaustion, which limit the therapeutic efficacy and persistence of CART cells. Here, we identified dasatinib as the optimal candidate to prevent or reverse both CD28/CART and 4-1BB/CART cell differentiation and exhaustion during ex vivo expansion, which profoundly enhanced the therapeutic efficacy and in vivo persistence. Moreover, strong activation-induced CART cells differentiation, exhaustion and apoptosis driven by CD3/CD28 stimulation or antigen exposure were dramatically prevented or reversed by dasatinib treatment. Mechanistically, dasatinib markedly reduced the phosphorylation of Src and Lck, and downregulated the expression of genes involved in CAR signaling pathways, which resulted in the optimization of cell differentiation, exhaustion and apoptosis-related gene expression. Our study proposes a promising pharmacological approach for optimizing CART cells manufacture, and provides an experimental basis for reinvigorating CART cells in clinical application.
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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.