ArticlePeerJ2022
Surface cysteine to serine substitutions in IL-18 reduce aggregation and enhance activity.
Article in PeerJ, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
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- Engineering an indoleamine 2,3-dioxygenase immunotherapyMolecular systems design & engineering · 2025Article
- Predicted IL-18/IL-18R Binding Improvement Through Protein Interface Modification with Computer-Aided Design.Biomolecules · 2025Article
- Engineered IL-18 variants with half-life extension and improved stability for cancer immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Targeting highly attenuated IL-18 to PD-1 for enhanced anti-tumor activity.Frontiers in immunology · 2025Article
- Role of Non-Binding T63 Alteration in IL-18 Binding.International journal of molecular sciences · 2024Article
- Article
- Next generation of multispecific antibody engineering.Antibody therapeutics · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Interleukin-18 (IL-18) is prone to form multimers resulting in inactive aggregates, making this cytokine unstable for clinical use. Therefore, mutations have been introduced into recombinant IL-18 to overcome this issue. Methods: To prevent the formation of disulfide bonds between the IL-18 molecules, multiple mutations targeting surface cysteines (C38, C68, C76, and C127) were introduced into our previously modified human IL-18 double mutant E6K+T63A (IL-18 DM) by direct gene synthesis. The open reading frames of IL-18 wild-type (WT), IL-18 DM, and IL-18 multiple mutant E6K+T63A+C38S+C68S+C76S+C127S (IL-18 DM1234) were inserted in the pET28a expression vector and transformed into Results: IL-18 DM1234 exhibited the lowest aggregation signal, approximately 1.79- and 1.63-fold less than that of the WT and IL-18 DM proteins. Additionally, the IFN-γ inducing activity of IL-18 DM1234 was about 10 and 2.8 times higher than that of the WT and IL-18 DM, respectively. MD simulations revealed that binding site I of IL-18 DM1234 was altered mainly due to surface cysteine replacement with serine (C-to-S substitution). This is the first report showing that C-to-S substitutions in IL-18 improved its activity and stability, suggesting the use of this modified IL-18 for medical purposes in the future.
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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.