ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
A Distinct Transcriptional Program in Human CAR T Cells Bearing the 4-1BB Signaling Domain Revealed by scRNA-Seq.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 107 citations in OpenAlex.
- Microfluidic-based rapid generation of chimeric antigen receptor T cells improves low-multiplicity-of-infection transduction efficiency while preserving functional activity.Journal of translational medicine · 2026Article
- Cell-based cancer immunotherapy: milestones, mechanistic insights, and emerging therapeutic directions.Acta pharmacologica Sinica · 2026Review
- Metabolic and functional analysis including repetitive antigen stimulation provides a more accurate assessment for CAR-T cell product quality and long-term functionality.Journal of translational medicine · 2026Article
- Transcriptomic landscape of peripheral T cells following CAR-T cell therapy in diffuse large B cell lymphoma.Cancer immunology, immunotherapy : CII · 2026Article
- Fate induction through asymmetric T cell division is modulated by chimeric antigen receptor costimulatory domains.Nature immunology · 2026Article
- BACH2 regulates T cell lineage state to enhance CAR T cell function.Nature immunology · 2026Article
- CD147 regulates CD8iScience · 2026Article
- CAR-adapted PIK3CD base editing enhances T cell anti-tumor potency.Nature cancer · 2026Article
- The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Navigating the landscape of personalized oncology: overcoming challenges and expanding horizons with computational modeling.Journal of the American Medical Informatics Association : JAMIA · 2026Article
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- Immune effector cell-associated neurotoxicity syndrome following CAR T-cell therapy: a review of recent advances.Journal of translational medicine · 2025Review
- Predictive markers for the efficacy of CAR T-cell therapy: the interplay between CAR T-cell fitness and systemic immunity.Blood advances · 2025Review
- Optimal pairing of binder and co-stimulatory domains improves dual CART cell efficacy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
- CD2 augmentation enhances CAR-T-cell efficacy via immunological synapse remodeling and T-cell exhaustion mitigation.Cellular & molecular immunology · 2025Article
- Comparison of axicabtagene ciloleucel and tisagenlecleucel patient CAR-T cell products by single-cell RNA sequencing.Journal for immunotherapy of cancer · 2025Article
- A universal chimeric antigen receptor (CAR)-fragment antibody binder (FAB) split system for cancer immunotherapy.Science advances · 2025Article
- Growth of human regulatory CD4iScience · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
T cells engineered to express chimeric antigen receptors (CARs) targeting CD19 have produced impressive outcomes for the treatment of B cell malignancies, but different products vary in kinetics, persistence, and toxicity profiles based on the co-stimulatory domains included in the CAR. In this study, we performed transcriptional profiling of bulk CAR T cell populations and single cells to characterize the transcriptional states of human T cells transduced with CD3ζ, 4-1BB-CD3ζ (BBζ), or CD28-CD3ζ (28ζ) co-stimulatory domains at rest and after activation by triggering their CAR or their endogenous T cell receptor (TCR). We identified a transcriptional signature common across CARs with the CD3ζ signaling domain, as well as a distinct program associated with the 4-1BB co-stimulatory domain at rest and after activation. CAR T cells bearing BBζ had increased expression of human leukocyte antigen (HLA) class II genes, ENPP2, and interleukin (IL)-21 axis genes, and decreased PD1 compared to 28ζ CAR T cells. Similar to previous studies, we also found BBζ CAR CD8 T cells to be enriched in a central memory cell phenotype and fatty acid metabolism genes. Our data uncovered transcriptional signatures related to costimulatory domains and demonstrated that signaling domains included in CARs uniquely shape the transcriptional programs of T cells.
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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.