ArticleScience translational medicine2017
TCR engagement negatively affects CD8 but not CD4 CAR T cell expansion and leukemic clearance.
Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 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.
The trial behind it
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
136 citing papers in PubMed, 205 citations in OpenAlex.
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Depletion of CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- The TCR in CAR T cell therapy: use it or lose it?Cancer gene therapy · 2026Review
- Distribution and prognostic value of T-cells in primary colorectal cancer and adjacent non-tumor mucosa in stage IV versus stage I-III patients.International journal of cancer · 2026Article
- Single-cell multiomics reveals regulatory mechanisms of CAR T-cell persistence and dysfunction in multiple myeloma.Blood neoplasia · 2026Article
- Rational redesign of antigen binding domain improves in vivo efficacy of the CD22-CAR.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- BACH2 dosage establishes the hierarchy of stemness and fine-tunes antitumor immunity in CAR T cells.Nature immunology · 2026Article
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- Adaptive-like CAR-iPSC-CD4⁺ T cells outperform CD8⁺ counterparts in sustained ALL control.Inflammation and regeneration · 2026Article
- Carbonic Anhydrase IX and Cyclooxygenase-2 Regulation in Renal Cell Carcinoma and Impact on Therapeutic Efficiency of Anti-CAIX CAR T cells.Current topics in medicinal chemistry · 2026Article
- Selective expansion and differentiation of antigen-specific CD4Drug delivery · 2025Article
- ProS1-MerTK signaling in CD4 T cells: implications for TIL expansion and functionality.Oncoimmunology · 2025Article
- Syngeneic CAR T cells engineered for persistent delivery of desired proteins.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Current status of chimeric antigen receptor T cell therapy and its exhaustion mechanism.Immunotherapy · 2025Review
- CAR T cell persistence in cancer.Trends in cancer · 2025Review
- Recent advances in universal chimeric antigen receptor T cell therapy.Journal of hematology & oncology · 2025Review
- Engineering resilient CAR T cells for immunosuppressive environment.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Mechanisms and Functions of γδ T Cells in Tumor Cell Recognition.Current oncology (Toronto, Ont.) · 2025Review
- Generating allogeneic CAR-NKT cells for off-the-shelf cancer immunotherapy with genetically engineered HSP cells and feeder-free differentiation culture.Nature protocols · 2025Review
- T-bet overexpression enhances CAR T cell effector functions and antigen sensitivity.Journal for immunotherapy of cancer · 2025Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR)-expressing T cells induce durable remissions in patients with relapsed/refractory B cell malignancies. CARs are synthetic constructs that, when introduced into mature T cells, confer a second, non-major histocompatibility complex-restricted specificity in addition to the endogenous T cell receptor (TCR). The implications of TCR activation on CAR T cell efficacy has not been well defined. Using an immunocompetent, syngeneic murine model of CD19-targeted CAR T cell therapy for pre-B cell acute lymphoblastic leukemia in which the CAR is introduced into T cells with known TCR specificity, we demonstrate loss of CD8 CAR T cell efficacy associated with T cell exhaustion and apoptosis when TCR antigen is present. CD4 CAR T cells demonstrate equivalent cytotoxicity to CD8 CAR T cells and, in contrast, retain in vivo efficacy despite TCR stimulation. Gene expression profiles confirm increased exhaustion and apoptosis of CD8 CAR T cells upon dual receptor stimulation compared to CD4 CAR T cells and indicate inherent differences between CD4 and CD8 CAR T cells in the use of T cell-associated signaling pathways. These results provide insights into important aspects of CAR T cell immune biology and indicate opportunities to rationally design CAR constructs to optimize clinical efficacy.
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What OpenQuestion holds
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.