ArticleImmunity2015
Interleukin-2 activity can be fine tuned with engineered receptor signaling clamps.
Article in Immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
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.
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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
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 176 citations in OpenAlex.
- A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases.EBioMedicine · 2023Pooled it
- CD25 genetic ablation on lymphoid cell lines to obtain models of stimulation through the Interleukin-2 beta/gamma receptor.Scientific reports · 2026Article
- Engineering trispecific IL-2 receptor agonistic antibodies through geometry optimization for enhanced Treg targeting.Nature communications · 2026Article
- Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics.Science (New York, N.Y.) · 2026Article
- Article
- Function-driven design of a surrogate interleukin-2 receptor ligand.FEBS letters · 2026Article
- Regulators of CD8Nature reviews. Immunology · 2026Review
- Miniaturized IL-2/anti-IL-2 immunocytokines selectively activate and support theFrontiers in immunology · 2026Article
- Protein engineering to overcome limitations of key cytokines in cancer immunotherapy: current approaches and future perspectives.Immuno-oncology technology · 2025Review
- Tuning of G-CSFR signaling by de novo-designed agonists.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- A CXCR4 partial agonist improves immunotherapy by targeting immunosuppressive neutrophils and cancer-driven granulopoiesis.Cancer cell · 2025Article
- Selectivity of bovine interleukin-2 mutein stimulation on bovine peripheral blood mononuclear cells.The Journal of veterinary medical science · 2025Article
- Regulating IL-2 Immune Signaling Function Via A Core Allosteric Structural Network.Journal of molecular biology · 2025Article
- Frontiers of cytokine engineering in CAR cell therapy for cancer.Frontiers in oncology · 2025Review
- 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
- Cytokine/Antibody Fusion Protein Design and Evaluation.Current protocols · 2024Article
- A CD25-biased interleukin-2 for autoimmune therapy engineered via a semi-synthetic organism.Communications medicine · 2024Article
- Molecular Engineering of Interleukin-2 for Enhanced Therapeutic Activity in Autoimmune Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
47 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
18 authors at 5 institutions in 1 country.
Funding
Abstract
Interleukin-2 (IL-2) regulates lymphocyte function by signaling through heterodimerization of the IL-2Rβ and γc receptor subunits. IL-2 is of considerable therapeutic interest, but harnessing its actions in a controllable manner remains a challenge. Previously, we have engineered an IL-2 "superkine" with enhanced affinity for IL-2Rβ. Here, we describe next-generation IL-2 variants that function as "receptor signaling clamps." They retained high affinity for IL-2Rβ, inhibiting binding of endogenous IL-2, but their interaction with γc was weakened, attenuating IL-2Rβ-γc heterodimerization. These IL-2 analogs acted as partial agonists and differentially affected lymphocytes poised at distinct activation thresholds. Moreover, one variant, H9-RETR, antagonized IL-2 and IL-15 better than blocking antibodies against IL-2Rα or IL-2Rβ. Furthermore, this mutein prolonged survival in a model of graft-versus-host disease and blocked spontaneous proliferation of smoldering adult T cell leukemia (ATL) T cells. This receptor-clamping approach might be a general mechanism-based strategy for engineering cytokine partial agonists for therapeutic immunomodulation.
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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.