ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Inhibition of Calcium Signaling Prevents Exhaustion and Enhances Anti-Leukemia Efficacy of CAR-T Cells via SOCE-Calcineurin-NFAT and Glycolysis Pathways.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
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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
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
- Calcineurin-mediated regulation of macrophage plasticity drives anti-tumor activity.Molecular therapy. Advances · 2026Article
- Bispecific Antibody-Based Combination Therapies for B-Cell Lymphomas: Current Evidence and Future Perspectives.International journal of cancer · 2026Review
- Linperlisib enhances MUC1-Tn CAR T cell efficacy by inhibiting EGR1/DUSP2 axis to prevent CAR T cell exhaustion.Leukemia · 2026Article
- EZH2 and intracellular CaCellular & molecular immunology · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mechanical preconditioning by shear stress enhances memory formation and anti-tumor function of CAR-T cells.Cancer immunology, immunotherapy : CII · 2026Article
- Engineering of genetically encoded programmable calcium channel inhibitory binders.Nature communications · 2026Article
- CAR-engineered cell therapies: current understandings and future perspectives.Molecular biomedicine · 2026Review
- Non-redundant functions of NFATc1 in survival and NFATc2 in generation of exhausted CD8Frontiers in immunology · 2026Article
- Mitochondria: from powerhouses of cells to hubs in antitumor immunity.Frontiers in immunology · 2026Review
- Metal Ions Within the Neuro-Immune-Tumor Axis.Journal of immunology research · 2026Review
- Dantrolene normalizes heightened CaCell calcium · 2025Article
- Glofitamab combined with tislelizumab in relapsed/refractory diffuse large B-cell lymphoma: a single-center pilot trial.Blood cancer journal · 2025Article
- Metal-modulated T cell antitumor immunity and emerging metalloimmunotherapy.Cancer metastasis reviews · 2025Review
- Presetting CAR-T cells during ex vivo biomanufacturing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Differential regulation of calcium-NFAT signaling pathway by Akt isoforms: unraveling effector dynamics and exhaustion of cytotoxic T lymphocytes in tumor microenvironment.Journal for immunotherapy of cancer · 2025Article
- Optimal chemokine receptors for enhancing immune cell trafficking in adoptive cell therapy.Immunologic research · 2025Article
- Sodium citrate pretreatment enhances CAR-T cell persistence and anti-tumor efficacy through inhibition of calcium signaling.Frontiers in immunology · 2025Article
- Current Advances and Challenges in CAR-T Therapy for Hematological and Solid Tumors.ImmunoTargets and therapy · 2025Review
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 potent agents for recognizing and eliminating tumors, and have achieved remarkable success in the treatment of patients with refractory leukemia and lymphoma. However, dysfunction of T cells, including exhaustion, is an inevitable obstacle for persistent curative effects. Here, the authors initially found that calcium signaling is hyperactivated via sustained tonic signaling in CAR-T cells. Next, it is revealed that the store-operated calcium entry (SOCE) inhibitor BTP-2, but not the calcium chelator BAPTA-AM, markedly diminishes CAR-T cell exhaustion and terminal differentiation of CAR-T cells in both tonic signaling and tumor antigen exposure models. Furthermore, BTP-2 pretreated CAR-T cells show improved antitumor potency and prolonged survival in vivo. Mechanistically, transcriptome and metabolite analyses reveal that treatment with BTP-2 significantly downregulate SOCE-calcineurin-nuclear factor of activated T-cells (NFAT) and glycolysis pathways. Together, the results indicate that modulating the SOCE-calcineurin-NFAT pathway in CAR-T cells renders them resistant to exhaustion, thereby yielding CAR products with enhanced antitumor potency.
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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.