ArticleCommunications biology2023
Molecular reshaping of phage-displayed Interleukin-2 at beta chain receptor interface to obtain potent super-agonists with improved developability profiles.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 6 citations in OpenAlex.
- CD25 genetic ablation on lymphoid cell lines to obtain models of stimulation through the Interleukin-2 beta/gamma receptor.Scientific reports · 2026Article
- A Convenient Strategy for Studying Antibody Aggregation and Inhibition of Aggregation: Characterization and Simulation.Pharmaceutics · 2025Article
- [Biological activity and antitumor effect of long-acting recombinant human interleukin-2 drug].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- Review
- 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
- Cytokine Couture: Designer IL2 Molecules for the Treatment of Disease.ImmunoTargets and therapy · 2025Review
- Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-2 (IL-2) engineered versions, with biased immunological functions, have emerged from yeast display and rational design. Here we reshaped the human IL-2 interface with the IL-2 receptor beta chain through the screening of phage-displayed libraries. Multiple beta super-binders were obtained, having increased receptor binding ability and improved developability profiles. Selected variants exhibit an accumulation of negatively charged residues at the interface, which provides a better electrostatic complementarity to the beta chain, and faster association kinetics. These findings point to mechanistic differences with the already reported superkines, characterized by a conformational switch due to the rearrangement of the hydrophobic core. The molecular bases of the favourable developability profile were tracked to a single residue: L92. Recombinant Fc-fusion proteins including our variants are superior to those based on H9 superkine in terms of expression levels in mammalian cells, aggregation resistance, stability, in vivo enhancement of immune effector responses, and anti-tumour effect.
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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.