ArticleCancer discovery2014
A small-molecule c-Rel inhibitor reduces alloactivation of T cells without compromising antitumor activity.
Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 57 citations in OpenAlex.
- Article
- APOE4 drives maladaptive heterogeneity and immunometabolic responses of astrocytes.Journal of neuroinflammation · 2026Article
- Design, synthesis and evaluation of pyrrolobenzodiazepine (PBD)-based PROTAC conjugates for the selective degradation of the NF-κB RelA/p65 subunit.RSC medicinal chemistry · 2025Article
- c-Rel is a Novel Oncogene in Lung Squamous Cell Carcinoma Regulating Cell Proliferation and Migration.Journal of Cancer · 2024Article
- Cytokine receptor IL27RA is an NF-κB-responsive gene involved in CD38 upregulation in multiple myeloma.Blood advances · 2023Article
- Dissecting the regulatory network of transcription factors in T cell phenotype/functioning during GVHD and GVT.Frontiers in immunology · 2023Review
- Inhibition of NF-κB DNA Binding Suppresses Myeloma Growth via Intracellular Redox and Tumor Microenvironment Modulation.Molecular cancer therapeutics · 2022Article
- The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target.Biomedicines · 2022Review
- Article
- Genome-Wide Association Study (GWAS) of dental caries in diverse populations.BMC oral health · 2021Article
- The role of small molecules in cell and gene therapy.RSC medicinal chemistry · 2021Review
- NF-κB in Cancer Immunity: Friend or Foe?Cells · 2021Review
- T Helper Cell Lineage-Defining Transcription Factors: Potent Targets for Specific GVHD Therapy?Frontiers in immunology · 2021Review
- c-Rel Is Required for IL-33-Dependent Activation of ILC2s.Frontiers in immunology · 2021Article
- c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis.Nature metabolism · 2020Article
- Recent Advances in Allogeneic CAR-T Cells.Biomolecules · 2020Review
- NF-κB/Rel Transcription Factors in Pancreatic Cancer: Focusing on RelA, c-Rel, and RelB.Cancers · 2019Review
- The Unsolved Puzzle of c-Rel in B Cell Lymphoma.Cancers · 2019Review
- Nrf2 regulates CD4Blood · 2018Article
- Chemical modulation of transcription factors.MedChemComm · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Preventing unfavorable GVHD without inducing broad suppression of the immune system presents a major challenge of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We developed a novel strategy to ameliorate GVHD while preserving graft-versus-tumor (GVT) activity by small molecule-based inhibition of the NF-κB family member c-Rel. Underlying mechanisms included reduced alloactivation, defective gut homing, and impaired negative feedback on interleukin (IL)-2 production, resulting in optimal IL-2 levels, which, in the absence of competition by effector T cells, translated into expansion of regulatory T cells. c-Rel activity was dispensable for antigen-specific T-cell receptor (TCR) activation, allowing c-Rel-deficient T cells to display normal GVT activity. In addition, inhibition of c-Rel activity reduced alloactivation without compromising antigen-specific cytotoxicity of human T cells. Finally, we were able to demonstrate the feasibility and efficacy of systemic c-Rel inhibitor administration. Our findings validate c-Rel as a promising target for immunomodulatory therapy and demonstrate the feasibility and efficacy of pharmaceutical inhibition of c-Rel activity.
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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.