ArticlemAbs
Generation and engineering of potent single domain antibody-based bispecific IL-18 mimetics resistant to IL-18BP decoy receptor inhibition.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Article
- Discovery and optimization of a pH-responsive ultra-long-acting VHH-based growth hormone mimetic.mAbs · 2026Article
- αTIGIT-guided IL-15 mimetics drive potent and safe antitumor immunity by restoring tumor-infiltrating T cells.Cellular & molecular immunology · 2026Article
- Simultaneous targeting of IL-10 and PD-(L)1 pathways with a bispecific anti-PD-L1/IL-10-trap antibody enhances T cell responses.Molecular therapy. Oncology · 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
- Antigen-directed single domain antibody-based TNFR1 agonists elicit preferential killing of HER2-overexpressing cancer cells.iScience · 2026Article
- Generation and Characterization of Bispecific VHH-Derived Surrogate Agonists Mimicking the Function of IL-18.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Generation and Characterization of Bispecific VHH-Derived Surrogate Agonists Mimicking the Function of IL-18.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Article
- Review
- Nanobody-engineered bispecific IL-18 mimetics drive antitumor immunity by engaging CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Structure-Guided Stapling of Dimeric Conformations and Linker Engineering Enhance Thermostability and Fine-Tune Activity of Bispecific VHH Cytokine Agonists.Antibodies (Basel, Switzerland) · 2025Article
- Taming interleukin-12: Engineering of bispecific antibody-based IL-12 mimetics with biased agonism capacities.Protein science : a publication of the Protein Society · 2025Article
- IL-18 and IL-18BP: A Unique Dyad in Health and Disease.International journal of molecular sciences · 2024Review
- On the humanization of VHHs: Prospective case studies, experimental and computational characterization of structural determinants for functionality.Protein science : a publication of the Protein Society · 2024Article
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- The potential of monoclonal antibodies for colorectal cancer therapy.Medical oncology (Northwood, London, England) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here, we generated bispecific antibody (bsAb) derivatives that mimic the function of interleukin (IL)-18 based on single domain antibodies (sdAbs) specific to IL-18 Rα and IL-18 Rβ. For this, camelids were immunized, followed by yeast surface display (YSD)-enabled discovery of VHHs targeting the individual receptor subunits. Upon reformatting into a strictly monovalent (1 + 1) bispecific sdAb architecture, several bsAbs triggered dose-dependent IL-18 R downstream signaling on IL-18 reporter cells, as well as IFN-γ release by peripheral blood mononuclear cells in the presence of low-dose IL-12. However, compared with IL-18, potencies and efficacies were considerably attenuated. By engineering paratope valencies and the spatial orientation of individual paratopes within the overall design architecture, we were able to generate IL-18 mimetics displaying significantly augmented functionalities, resulting in bispecific cytokine mimetics that were more potent than IL-18 in triggering proinflammatory cytokine release. Furthermore, generated IL-18 mimetics were unaffected from inhibition by IL-18 binding protein decoy receptor. Essentially, we demonstrate that this strategy enables the generation of IL-18 mimetics with tailor-made cytokine functionalities.
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.