ArticleCell reports2017
Tonic 4-1BB Costimulation in Chimeric Antigen Receptors Impedes T Cell Survival and Is Vector-Dependent.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
184 citing papers in PubMed, 271 citations in OpenAlex.
- CRISPRa screen unveils noncanonical NF-κB to boost the antitumor activity of TCR-based CAR-T cells.Cellular & molecular immunology · 2026Article
- Gene regulatory elements determine efficacy of BCMA-targeted CAR-T cell products.Journal for immunotherapy of cancer · 2026Article
- Recent advances in molecular mechanisms to improve the efficacy of CAR-T cell therapy for viral diseases, cancer, and autoimmune diseases.Stem cell research & therapy · 2026Review
- From Delivery to Design: Site-Specific Genome Engineering for Next-Generation CAR T-Cell Therapy.Biomedicines · 2026Review
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- Impaired hematopoiesis affects apheresis and CAR T-cell product composition and treatment response.Transfusion · 2026Article
- Fate induction through asymmetric T cell division is modulated by chimeric antigen receptor costimulatory domains.Nature immunology · 2026Article
- CCR5-targeted allogeneic gamma-delta CD19 chimeric antigen receptor T cells for HIV-associated B cell-malignancy immunotherapy.Nature biomedical engineering · 2026Article
- Emerging Applications of CAR-T Cell Therapy in Overcoming Resistance and Expanding Targets in Hematologic Malignancies: Insights from Recent Research.Current treatment options in oncology · 2026Review
- Engineering CAR-Vδ2 T cells to boost persistence and anti-tumor function.bioRxiv : the preprint server for biology · 2026Article
- Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cells.Nature biomedical engineering · 2026Article
- FcεRγI promotes canine CD8 chimeric antigen receptor T cell cytotoxicity through a Syk-NF-κB axis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Are we there yet? The road to faster and more efficient CAR T cell manufacturing.Journal of biological engineering · 2026Review
- Enhancing CAR- and TCR-mediated targeting of cancer via an immune synapse-stabilizing receptor.Nature communications · 2026Article
- A motif-vocabulary model of CAR T-cell intracellular domains identifies determinants of immunophenotype differentiation.bioRxiv : the preprint server for biology · 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
- CAR Intrinsic Design Pre-Shapes Transcriptional and Metabolic Networks in CAR T Cells.Metabolites · 2026Article
- T cell exhaustion landscapes and therapeutic modulation in cancer immunity.Frontiers in cell and developmental biology · 2026Review
- Review
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
124 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
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Antigen-independent tonic signaling by chimeric antigen receptors (CARs) can increase differentiation and exhaustion of T cells, limiting their potency. Incorporating 4-1BB costimulation in CARs may enable T cells to resist this functional exhaustion; however, the potential ramifications of tonic 4-1BB signaling in CAR T cells remain unclear. Here, we found that tonic CAR-derived 4-1BB signaling can produce toxicity in T cells via continuous TRAF2-dependent activation of the nuclear factor κB (NF-κB) pathway and augmented FAS-dependent cell death. This mechanism was amplified in a non-self-inactivating gammaretroviral vector through positive feedback on the long terminal repeat (LTR) promoter, further enhancing CAR expression and tonic signaling. Attenuating CAR expression by substitution with a self-inactivating lentiviral vector minimized tonic signaling and improved T cell expansion and anti-tumor function. These studies illuminate the interaction between tonic CAR signaling and the chosen expression platform and identify inhibitory properties of the 4-1BB costimulatory domain that have direct implications for rational CAR design.
Indexed as
Identifiers
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.