ArticleBlood advances2020
The S enantiomer of 2-hydroxyglutarate increases central memory CD8 populations and improves CAR-T therapy outcome.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Metabolic Bottlenecks and Opportunities: Reshaping the Tumor Microenvironment for Cancer Immunotherapy.Cells · 2026Review
- Epigenetic editing to advance CAR T cell therapy.Clinical epigenetics · 2026Review
- Pomalidomide enhances CAR-T cell therapeutic efficacy and remodels immune microenvironment in lymphoid malignancies.Cancer immunology, immunotherapy : CII · 2025Article
- Immunometabolite L-2-HG promotes epigenetic modification of exhausted T cells and improves antitumor immunity.JCI insight · 2025Article
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Article
- Review
- Glutarate tunes T cell fate.Nature metabolism · 2023Article
- Glutarate regulates T cell metabolism and anti-tumour immunity.Nature metabolism · 2023Article
- The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function.Cell reports · 2023Article
- Review
- Crosstalk between autophagy and metabolic regulation of (CAR) T cells: therapeutic implications.Frontiers in immunology · 2023Review
- Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy.Frontiers in immunology · 2023Review
- DIALing-up the preclinical characterization of gene-modified adoptive cellular immunotherapies.Frontiers in immunology · 2023Review
- The mitochondrial pyruvate carrier regulates memory T cell differentiation and antitumor function.Cell metabolism · 2022Article
- Mutant IDH Inhibits IFNγ-TET2 Signaling to Promote Immunoevasion and Tumor Maintenance in Cholangiocarcinoma.Cancer discovery · 2022Article
- Review
- Epigenetic strategies to boost CAR T cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Tinkering under the Hood: Metabolic Optimisation of CAR-T Cell Therapy.Antibodies (Basel, Switzerland) · 2021Review
- Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Cancer immunotherapy is advancing rapidly and gene-modified T cells expressing chimeric antigen receptors (CARs) show particular promise. A challenge of CAR-T cell therapy is that the ex vivo-generated CAR-T cells become exhausted during expansion in culture, and do not persist when transferred back to patients. It has become clear that naive and memory CD8 T cells perform better than the total CD8 T-cell populations in CAR-T immunotherapy because of better expansion, antitumor activity, and persistence, which are necessary features for therapeutic success and prevention of disease relapse. However, memory CAR-T cells are rarely used in the clinic due to generation challenges. We previously reported that mouse CD8 T cells cultured with the S enantiomer of the immunometabolite 2-hydroxyglutarate (S-2HG) exhibit enhanced antitumor activity. Here, we show that clinical-grade human donor CAR-T cells can be generated from naive precursors after culture with S-2HG. S-2HG-treated CAR-T cells establish long-term memory cells in vivo and show superior antitumor responses when compared with CAR-T cells generated with standard clinical protocols. This study provides the basis for a phase 1 clinical trial evaluating the activity of S-2HG-treated CD19-CAR-T cells in patients with B-cell malignancies.
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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.