ArticleOncoTargets and therapy2018
Metformin inhibits proliferation and cytotoxicity and induces apoptosis via AMPK pathway in CD19-chimeric antigen receptor-modified T cells.
Article in OncoTargets and therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Targeting metabolic reprogramming to enhance adoptive immunotherapy: emerging mechanisms and translational perspectives.Journal of translational medicine · 2026Review
- Senotherapeutic repurposing of metformin for age-related diseases and their signaling pathways.Molecular biology reports · 2025Review
- Enhancing CAR-T Cell Metabolic Fitness and Memory Phenotype for Improved Efficacy against Hepatocellular Carcinoma.International journal of biological sciences · 2025Article
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Intrinsic ADRB2 inhibition improves CAR-T cell therapy efficacy against prostate cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- CAR T cell infiltration and cytotoxic killing within the core of 3D breast cancer spheroids under the control of antigen sensing in microwell arrays.APL bioengineering · 2024Article
- Enhancing CAR T cells function: role of immunomodulators in cancer immunotherapy.Clinical and experimental medicine · 2024Review
- Enhancing CAR-T cell metabolism to overcome hypoxic conditions in the brain tumor microenvironment.JCI insight · 2024Article
- Chimeric Antigen Receptor (CAR)-Based Cell Therapy for Type 1 Diabetes Mellitus (T1DM); Current Progress and Future Approaches.Stem cell reviews and reports · 2024Review
- Patient-derived bladder cancer organoid model to predict sensitivity and feasibility of tailored precision therapy.Current urology · 2023Article
- Hyaluronic Acid-Coated Chitosan/Gelatin Nanoparticles as a New Strategy for Topical Delivery of Metformin in Melanoma.BioMed research international · 2023Article
- Crosstalk between autophagy and metabolic regulation of (CAR) T cells: therapeutic implications.Frontiers in immunology · 2023Review
- Metformin and Cancer, an Ambiguanidous Relationship.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Barriers to Immunotherapy in Ovarian Cancer: Metabolic, Genomic, and Immune Perturbations in the Tumour Microenvironment.Cancers · 2021Review
- Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies.Molecular and cellular biochemistry · 2021Article
- Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts.Journal of translational medicine · 2021Article
- Inflammatory myofibroblastic tumor successfully treated with metformin: A case report and review of literature.World journal of clinical cases · 2021Article
- Obesity and CD8 T cell metabolism: Implications for anti-tumor immunity and cancer immunotherapy outcomes.Immunological reviews · 2020Review
- [Research Advance in Anti-lung Cancer Mechanism of Metformin].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2020Review
- Competitive glucose metabolism as a target to boost bladder cancer immunotherapy.Nature reviews. Urology · 2020Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCD19-chimericantigen receptor (CAR) modified T cells (CD19-CAR T cells) have been well documented to possess potent anti-tumor properties against CD19-expressingleukemia cells. As a traditional medicine, metformin has been widely used to treat type II diabetes mellitus and more recently has become a candidate for the treatment of cancer. However, no report has revealed the direct effect of metformin on CD19-CAR T cell biological function and its underling mechanisms. PURPOSE: The purpose of this research was to explore the effect of metformin on CD19-CAR T cell biological function and the mechanisms involved.
methodsCD19-CAR T cells proliferation, apoptosis and cytotoxicity were mainly tested by CCK-8 assay, flow cytometry and ELISA. The detection of mechanism primarily used western blot. Bioluminescence imaging is the main application technology of animal studies.
resultsIn the current study, it was found that metformin inhibited CD19-CAR T cell proliferation and cytotoxicity and induced apoptosis. Furthermore, our study revealed that metformin activated AMPK and suppressed mTOR and HIF1α expression. By using an AMPK inhibitor, compound C, we demonstrated the crucial roles of AMPK in CD19-CAR T cells when they were treated with metformin. Finally, we verified that metformin suppressed the cytotoxicity of CD19-CAR T cell in vivo.
conclusionTaken together, these results indicated that metformin may play an important role in modulating CD19-CAR T cell biological functions in an AMPK-dependent and mTOR/HIF1α-independent manner.
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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.