Coupling of aggregation and immunogenicity in biotherapeutics: T- and B-cell immune epitopes may contain aggregation-prone regions
Abstract
Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregation prone regions as well as T- and B-cell immune epitopes from protein sequence and structure have become available recently. Here, we describe a potential coupling between aggregation and immunogenicity: T-cell and B-cell immune epitopes in therapeutic proteins may contain aggregation-prone regions. The details of biological mechanisms behind this observation remain to be understood. However, our observation opens up an exciting potential for rational design of de-immunized novel, as well as follow on biotherapeutics with reduced aggregation propensity.
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Kumar and co-workers have observed an overlap between potential immune epitopes and aggregation prone regions (APRs) around the CDRs of therapeutic antibodies.
“Kumar and co-workers have observed an overlap between potential immune epitopes and aggregation prone regions (APRs) around the CDRs of therapeutic antibodies [195, 196].”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [195]
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Computational approaches to therapeutic antibody design: established methods and emerging trends
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- Authors
- Kumar, S., Singh, S. K., Wang, X., Rup, B., & Gill, D.
- Affiliations
- Pfizer (United States) (US)
- Corresponding author
- Kumar, Sandeep
- Venue
- Pharmaceutical Research
- Published
- 2011-03-25
- Volume
- 28
- Issue
- 5
- Pages
- 949-961
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W2054738095
- Cited by
- 85
- References
- 52
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 5 · 2016: 5 · 2015: 13 · 2014: 5 · 2013: 7 · 2012: 15
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- biologic therapy, protein aggregation, immunogenicity, T cell epitopes, B-cell epitopes, aggregation-prone regions, epitope prediction, rational design, therapeutic antibodies, recombinant protein
- MeSH terms
- Amino Acid Sequence, Animals, Biological Products, Humans, Models, Molecular, Molecular Sequence Data, Proteins, Epitopes, T-Lymphocyte, Epitopes, B-Lymphocyte, Drug Discovery
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