ArticleLeukemia2023
Culture expansion of CAR T cells results in aberrant DNA methylation that is associated with adverse clinical outcome.
Article in Leukemia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
17 citing papers in PubMed, 26 citations in OpenAlex.
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Implications of Rho GTPase signaling in cancer immunotherapy.Biochemical Society transactions · 2026Review
- Secondary malignancy of T-cell origin after CAR T-cell therapy: EMA's conclusions from the evaluation of 38 suspected cases.Gene therapy · 2026Article
- Are we there yet? The road to faster and more efficient CAR T cell manufacturing.Journal of biological engineering · 2026Review
- Histological grade 2 and non-contrast-enhancing phenotype provide prognostic information complementary to DNA methylation classification in TERTp-mutant molecular glioblastomas.Acta neuropathologica communications · 2026Article
- Genome-Wide Blood DNA Methylation Profiling in Birch Pollen Allergic Patients Undergoing Allergen-Specific Immunotherapy.Allergy · 2025Article
- In vivo CAR-T cell engineering: concept, research progress, potential challenges and enhancement strategies.Experimental hematology & oncology · 2025Review
- Label-free estimation of regulatory T cell activation markers using Raman spectroscopy with machine learning.Scientific reports · 2025Article
- Epigenetic editing at individual age-associated CpGs affects the genome-wide epigenetic aging landscape.Nature aging · 2025Article
- DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities.Clinical epigenetics · 2025Review
- Advances in strategies to improve the immunotherapeutic efficacy of chimeric antigen receptor-T cell therapy for lymphoma.Cancer biology & medicine · 2025Review
- Characterization of Rationally Designed CRISPR/Cas9-Based DNA Methyltransferases with Distinct Methyltransferase and Gene Silencing Activities in Human Cell Lines and Primary Human T Cells.ACS synthetic biology · 2025Article
- Stable Transmission of DNA Methylation Epimutations from Germlines to the Liver and Their Association with Fatty Liver Disease in Medaka.Research square · 2025Article
- CAR T-cell-associated secondary malignancies challenge current pharmacovigilance concepts.EMBO molecular medicine · 2025Review
- Getting the right combination to break the epigenetic code.Nature reviews. Clinical oncology · 2025Review
- New insights on potency assays from recent advances and discoveries in CAR T-cell therapy.Frontiers in immunology · 2025Review
- A digital shadow of CAR T cell expansion in a perfusion bioreactor: Informing optimal harvest times for autologous cell therapy.Biotechnology progressArticle
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR) T cells provide new perspectives for treatment of hematological malignancies. Manufacturing of these cellular products includes culture expansion procedures, which may affect cellular integrity and therapeutic outcome. In this study, we investigated culture-associated epigenetic changes in CAR T cells and found continuous gain of DNAm, particularly within genes that are relevant for T cell function. Hypermethylation in many genes, such as TCF7, RUNX1, and TOX, was reflected by transcriptional downregulation. 332 CG dinucleotides (CpGs) showed an almost linear gain in methylation with cell culture time, albeit neighboring CpGs were not coherently regulated on the same DNA strands. An epigenetic signature based on 14 of these culture-associated CpGs predicted cell culture time across various culture conditions. Notably, even in CAR T cell products of similar culture time higher DNAm levels at these CpGs were associated with significantly reduced long-term survival post transfusion. Our data demonstrate that cell culture expansion of CAR T cells evokes DNA hypermethylation at specific sites in the genome and the signature may also reflect loss of potential in CAR T cell products. Hence, reduced cultivation periods are beneficial to avoid dysfunctional methylation programs that seem to be associated with worse therapeutic outcome.
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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 Socratic graph.