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Published on: March 8, 2024
Immunoengineering approaches for cytokine therapy
Aslan Mansurov1, Abigail Lauterbach1, Erica Budina1
1Pritzker School of Molecular Engineering, University of Chicago, Chicago, Illinois.
Abstract:
Since the discovery of cytokines, much effort has been put forth to achieve therapeutic translation for treatment of various diseases, including cancer and autoimmune diseases. Despite these efforts, very few cytokines have cleared regulatory approval, and those that were approved are not commonly used due to their challenging toxicity profile and/or limited therapeutic efficacy. The main limitation in translation has been that wild-type cytokines have unfavorable pharmacokinetic and pharmacodynamic profiles, either eliciting unwanted systemic side effects or insufficient residence in secondary lymphoid organs. In this review, we address protein-engineering approaches that have been applied to both proinflammatory and anti-inflammatory cytokines to enhance their therapeutic indices, and we highlight diseases in which administration of engineered cytokines is especially relevant.
Insights
Protein engineering improves therapeutic cytokines for cancer and autoimmune diseases. Modified cytokines offer better safety and efficacy than wild-type versions, overcoming previous limitations.
Area of Science:
- Biotechnology
- Immunology
- Drug Development
Background:
- Cytokines are crucial signaling molecules with therapeutic potential for cancer and autoimmune diseases.
- Current cytokine therapies face challenges with toxicity, limited efficacy, and unfavorable pharmacokinetics.
- Wild-type cytokines often cause systemic side effects or do not remain in target organs long enough.
Purpose of the Study:
- To review protein-engineering strategies for enhancing cytokine therapeutic indices.
- To highlight the relevance of engineered cytokines in treating specific diseases.
- To address limitations of wild-type cytokines in clinical applications.
Main Methods:
- Review of protein-engineering techniques applied to cytokines.
- Analysis of pharmacokinetic and pharmacodynamic improvements.
- Examination of clinical relevance in various disease contexts.
Main Results:
- Protein engineering can significantly enhance cytokine therapeutic efficacy and safety.
- Modified cytokines demonstrate improved residence time in secondary lymphoid organs.
- Engineered cytokines offer a promising alternative to wild-type versions.
Conclusions:
- Protein engineering is a viable strategy to overcome the limitations of cytokine therapeutics.
- Engineered cytokines hold significant promise for treating cancer and autoimmune disorders.
- Further development of engineered cytokines could expand their clinical application.
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