ArticleJournal of immunotherapy (Hagerstown, Md. : 1997)
Engineered interleukin-2 antagonists for the inhibition of regulatory T cells.
Article in Journal of immunotherapy (Hagerstown, Md. : 1997). The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 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
28 citing papers in PubMed, 43 citations in OpenAlex.
- Regulating IL-2 Immune Signaling Function Via A Core Allosteric Structural Network.Journal of molecular biology · 2025Article
- Cytokine Couture: Designer IL2 Molecules for the Treatment of Disease.ImmunoTargets and therapy · 2025Review
- Directed disruption of IL2 aggregation and receptor binding sites produces designer biologics with enhanced specificity and improved production capacity.Computational and structural biotechnology journal · 2025Article
- The JAK-STAT pathway: from structural biology to cytokine engineering.Signal transduction and targeted therapy · 2024Review
- Molecular Engineering of Interleukin-2 for Enhanced Therapeutic Activity in Autoimmune Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies.Molecular cancer · 2023Review
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
- Emerging principles of cytokine pharmacology and therapeutics.Nature reviews. Drug discovery · 2023Review
- Intratumoral nanobody-IL-2 fusions that bind the tumor extracellular matrix suppress solid tumor growth in mice.PNAS nexus · 2022Article
- Engineering IL-2 for immunotherapy of autoimmunity and cancer.Nature reviews. Immunology · 2022Review
- Site-specific PEGylation of interleukin-2 enhances immunosuppression via the sustained activation of regulatory T cells.Nature biomedical engineering · 2021Article
- An engineered IL-2 partial agonist promotes CD8Nature · 2021Article
- Radiolabelling anReaction chemistry & engineering · 2021Article
- Effects of interleukin-2 in immunostimulation and immunosuppression.The Journal of experimental medicine · 2020Review
- Directed evolution of super-secreted variants from phage-displayed human Interleukin-2.Scientific reports · 2019Article
- IL-2 and Beyond in Cancer Immunotherapy.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2018Review
- Reprogramming cellular functions with engineered membrane proteins.Current opinion in biotechnology · 2017Review
- Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells.Nature communications · 2017Article
- Article
- pH responsive granulocyte colony-stimulating factor variants with implications for treating Alzheimer's disease and other central nervous system disorders.Protein engineering, design & selection : PEDS · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The immunosuppressive effects of CD4+ CD25 high regulatory T cells (Tregs) interfere with antitumor immune responses in cancer patients. Here, we present a novel class of engineered human interleukin (IL)-2 analogs that antagonizes the IL-2 receptor, for inhibiting regulatory T cell suppression. These antagonists have been engineered for high affinity to the alpha subunit of the IL-2 receptor and very low affinity to either the beta or gamma subunit, resulting in a signaling-deficient IL-2 analog that sequesters the IL-2 receptor alpha subunit from wild type IL-2. Two variants, "V91R" and "Q126T" with residue substitutions that disrupt the beta and gamma subunit binding interfaces, respectively, have been characterized in both a T cell line and in human primary Tregs. These mutants retain their high affinity binding to IL-2 receptor alpha subunit, but do not activate STAT5 phosphorylation or stimulate T cell growth. The 2 mutants competitively antagonize wild-type IL-2 signaling through the IL-2 receptor with similar efficacy, with inhibition constants of 183 pM for V91R and 216 pM for Q126T. Here, we present a novel approach to CD25-mediated Treg inhibition, with the use of an engineered human IL-2 analog that antagonizes the IL-2 receptor.
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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.