ArticleCells2024
Modulating Cholesterol Metabolism via ACAT1 Knockdown Enhances Anti-B-Cell Lymphoma Activities of CD19-Specific Chimeric Antigen Receptor T Cells by Improving the Cell Activation and Proliferation.
Article in Cells, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- Obesity and diabetes associated with dysregulation of mevalonate pathway markers and progression from pancreatic intraepithelial neoplasia to invasive pancreatic tumor.Stem cell research & therapy · 2026Article
- High-Content SRS Imaging Unveils Altered Cholesterol Metabolism in Ovarian Cancers Under CAR-T Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting metabolic reprogramming to enhance adoptive immunotherapy: emerging mechanisms and translational perspectives.Journal of translational medicine · 2026Review
- TIPE2 knockdown enhances the anti-tumor efficacy of NKG2D CAR-T cells against pancreatic cancer via activating NF-κb signaling pathway.Journal of translational medicine · 2026Article
- Review
- Advanced strategies to enhance the safety, persistence, and efficacy of CAR-T cells in solid tumors.Frontiers in immunology · 2026Review
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
- Advances in strategies to improve the immunotherapeutic efficacy of chimeric antigen receptor-T cell therapy for lymphoma.Cancer biology & medicine · 2025Review
- Mitochondrial cholesterol metabolism related gene model predicts prognosis and treatment response in hepatocellular carcinoma.Translational cancer research · 2024Article
- shRNA-mediated gene silencing of HDAC11 empowers CAR-T cells against prostate cancer.Frontiers in immunology · 2024Article
- The Pan-Cancer Analysis Uncovers the Prognostic and Immunotherapeutic Significance of CD19 as an Immune Marker in Tumor.International journal of general medicine · 2024Article
- Autologous stem cell transplantation meets CAR-T therapy: A synergistic strategy for B-cell lymphoma.Cell transplantationReview
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
CD19-specific CAR-T immunotherapy has been extensively studied for the treatment of B-cell lymphoma. Recently, cholesterol metabolism has emerged as a modulator of T lymphocyte function and can be exploited in immunotherapy to increase the efficacy of CAR-based systems. Acetyl-CoA acetyltransferase 1 (ACAT1) is the major cholesterol esterification enzyme. ACAT1 inhibitors previously shown to modulate cardiovascular diseases are now being implicated in immunotherapy. In the present study, we achieved knockdown of ACAT1 in T cells via RNA interference technology by inserting ACAT1-shRNA into anti-CD19-CAR-T cells. Knockdown of ACAT1 led to an increased cytotoxic capacity of the anti-CD19-CAR-T cells. In addition, more CD69, IFN-γ, and GzmB were expressed in the anti-CD19-CAR-T cells. Cell proliferation was also enhanced in both antigen-independent and antigen-dependent manners. Degranulation was also improved as evidenced by an increased level of CD107a. Moreover, the knockdown of ACAT1 led to better anti-tumor efficacy of anti-CD19 CAR-T cells in the B-cell lymphoma mice model. Our study demonstrates novel CAR-T cells containing ACAT1 shRNA with improved efficacy compared to conventional anti-CD19-CAR-T cells in vitro and in vivo.
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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.