ArticleCell2022
Facile discovery of surrogate cytokine agonists.
Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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
56 citing papers in PubMed, 74 citations in OpenAlex.
- Article
- Discovery and optimization of a pH-responsive ultra-long-acting VHH-based growth hormone mimetic.mAbs · 2026Article
- Article
- Article
- αTIGIT-guided IL-15 mimetics drive potent and safe antitumor immunity by restoring tumor-infiltrating T cells.Cellular & molecular immunology · 2026Article
- Realizing the potential of agonistic antibody immunotherapy.Nature reviews. Drug discovery · 2026Review
- Protocol for in vitro profiling of key TNF downstream signaling pathways involved in cell death and pro-survival signaling in cancer cells.STAR protocols · 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
- Antigen-directed single domain antibody-based TNFR1 agonists elicit preferential killing of HER2-overexpressing cancer cells.iScience · 2026Article
- Function-driven design of a surrogate interleukin-2 receptor ligand.FEBS letters · 2026Article
- IL-10's contextual role in cytotoxic antitumor immunity: evidence, controversies, and therapeutic translation.Frontiers in immunology · 2026Review
- Review
- Tuning of G-CSFR signaling by de novo-designed agonists.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- High-Throughput De Novo Protein Design Yields Novel Immunomodulatory Agonists.bioRxiv : the preprint server for biology · 2025Article
- Geometric Tuning of Cytokine Receptor Association Modulates Synthetic Agonist Signaling.bioRxiv : the preprint server for biology · 2025Article
- Fifty years of monoclonals: the past, present and future of antibody therapeutics.Nature reviews. Immunology · 2025Article
- Design of a potent interleukin-21 mimic for cancer immunotherapy.Science immunology · 2025Article
- Article
Corrections and comments
- Commented on by
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Cytokines are powerful immune modulators that initiate signaling through receptor dimerization, but natural cytokines have structural limitations as therapeutics. We present a strategy to discover cytokine surrogate agonists by using modular ligands that exploit induced proximity and receptor dimer geometry as pharmacological metrics amenable to high-throughput screening. Using VHH and scFv to human interleukin-2/15, type-I interferon, and interleukin-10 receptors, we generated combinatorial matrices of single-chain bispecific ligands that exhibited diverse spectrums of functional activities, including potent inhibition of SARS-CoV-2 by surrogate interferons. Crystal structures of IL-2R:VHH complexes revealed that variation in receptor dimer geometries resulted in functionally diverse signaling outputs. This modular platform enabled engineering of surrogate ligands that compelled assembly of an IL-2R/IL-10R heterodimer, which does not naturally exist, that signaled through pSTAT5 on T and natural killer (NK) cells. This "cytokine med-chem" approach, rooted in principles of induced proximity, is generalizable for discovery of diversified agonists for many ligand-receptor systems.
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.