ArticleJournal of the National Cancer Institute2022
Epigenetic Profiling and Response to CD19 Chimeric Antigen Receptor T-Cell Therapy in B-Cell Malignancies.
Article in Journal of the National Cancer Institute, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Biomarkers for predicting CAR-T cell therapy outcomes in B-cell acute lymphoblastic leukemia: a systematic review.Frontiers in immunology · 2025Pooled it
- Epigenetic insights and innovations for overcoming barriers in CAR-T cell therapy for cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Anti-CD19 CAR T cells for pediatric patients with treatment-refractory autoimmune diseases.Nature medicine · 2026Article
- DNA methylation and transcription factor-driven immune subtypes in ovarian cancer.Discover oncology · 2025Article
- Prior chemotherapy deteriorates T-cell quality for CAR T-cell therapy in B-cell non-Hodgkin's lymphoma.Journal for immunotherapy of cancer · 2025Article
- Genetic immune escape in cancer: timing and implications for treatment.Trends in cancer · 2025Review
- CAR-T therapy dilemma and innovative design strategies for next generation.Cell death & disease · 2025Review
- Mechanisms of antigen-dependent resistance to chimeric antigen receptor (CAR)-T cell therapies.Cancer cell international · 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
- Unlocking the Role of Treg Cells Immune Response and Infectious Risk Following CAR T-Cell Therapy in Patients with Cancer.International journal of molecular sciences · 2025Review
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- New insights on potency assays from recent advances and discoveries in CAR T-cell therapy.Frontiers in immunology · 2025Review
- Advances in epigenetic therapies for B-cell non-hodgkin lymphoma.Annals of hematology · 2024Review
- Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review.International journal of molecular sciences · 2024Review
- Regulation of CAR transgene expression to design semiautonomous CAR-T.Molecular therapy. Oncology · 2024Review
- Development of an epigenetic clock resistant to changes in immune cell composition.Communications biology · 2024Article
- Unveiling the Influence of AI Predictive Analytics on Patient Outcomes: A Comprehensive Narrative Review.Cureus · 2024Review
- Culture expansion of CAR T cells results in aberrant DNA methylation that is associated with adverse clinical outcome.Leukemia · 2023Article
- Reshaping the tumour immune microenvironment in solid tumours via tumour cell and immune cell DNA methylation: from mechanisms to therapeutics.British journal of cancer · 2023Review
- RE: COVID-19 severity by vaccination status in the NCI COVID-19 and Cancer Patients Study (NCCAPS).Journal of the National Cancer Institute · 2023Article
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Authors and funding
26 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChimeric antigen receptor (CAR) T cells directed against CD19 (CART19) are effective in B-cell malignancies, but little is known about the molecular factors predicting clinical outcome of CART19 therapy. The increasingly recognized relevance of epigenetic changes in cancer immunology prompted us to determine the impact of the DNA methylation profiles of CART19 cells on the clinical course.
methodsWe recruited 114 patients with B-cell malignancies, comprising 77 patients with acute lymphoblastic leukemia and 37 patients with non-Hodgkin lymphoma who were treated with CART19 cells. Using a comprehensive DNA methylation microarray, we determined the epigenomic changes that occur in the patient T cells upon transduction of the CAR vector. The effects of the identified DNA methylation sites on clinical response, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, event-free survival, and overall survival were assessed. All statistical tests were 2-sided.
resultsWe identified 984 genomic sites with differential DNA methylation between CAR-untransduced and CAR-transduced T cells before infusion into the patient. Eighteen of these distinct epigenetic loci were associated with complete response (CR), adjusting by multiple testing. Using the sites linked to CR, an epigenetic signature, referred to hereafter as the EPICART signature, was established in the initial discovery cohort (n = 79), which was associated with CR (Fisher exact test, P < .001) and enhanced event-free survival (hazard ratio [HR] = 0.36; 95% confidence interval [CI] = 0.19 to 0.70; P = .002; log-rank P = .003) and overall survival (HR = 0.45; 95% CI = 0.20 to 0.99; P = .047; log-rank P = .04;). Most important, the EPICART profile maintained its clinical course predictive value in the validation cohort (n = 35), where it was associated with CR (Fisher exact test, P < .001) and enhanced overall survival (HR = 0.31; 95% CI = 0.11 to 0.84; P = .02; log-rank P = .02).
conclusionsWe show that the DNA methylation landscape of patient CART19 cells influences the efficacy of the cellular immunotherapy treatment in patients with B-cell malignancy.
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