![](/images/graphics-bg.png)
The Role of Aggregates of Therapeutic Protein Products in Immunogenicity: An Evaluation by Mathematical Modeling
Joint Authors
Yin, Liusong
Chen, Xiaoying
Tiwari, Abhinav
Vicini, Paolo
Hickling, Timothy P.
Source
Journal of Immunology Research
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-11-22
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Therapeutic protein products (TPP) have been widely used to treat a variety of human diseases, including cancer, hemophilia, and autoimmune diseases.
However, TPP can induce unwanted immune responses that can impact both drug efficacy and patient safety.
The presence of aggregates is of particular concern as they have been implicated in inducing both T cell-independent and T cell-dependent immune responses.
We used mathematical modeling to evaluate several mechanisms through which aggregates of TPP could contribute to the development of immunogenicity.
Modeling interactions between aggregates and B cell receptors demonstrated that aggregates are unlikely to induce T cell-independent immune responses by cross-linking B cell receptors because the amount of signal transducing complex that can form under physiologically relevant conditions is limited.
We systematically evaluate the role of aggregates in inducing T cell-dependent immune responses using a recently developed multiscale mechanistic mathematical model.
Our analysis indicates that aggregates could contribute to T cell-dependent immune response by inducing high affinity epitopes which may not be present in the nonaggregated TPP and/or by enhancing danger signals to break tolerance.
In summary, our computational analysis is suggestive of novel insights into the mechanisms underlying aggregate-induced immunogenicity, which could be used to develop mitigation strategies.
American Psychological Association (APA)
Yin, Liusong& Chen, Xiaoying& Tiwari, Abhinav& Vicini, Paolo& Hickling, Timothy P.. 2015. The Role of Aggregates of Therapeutic Protein Products in Immunogenicity: An Evaluation by Mathematical Modeling. Journal of Immunology Research،Vol. 2015, no. 2015, pp.1-14.
https://search.emarefa.net/detail/BIM-1068468
Modern Language Association (MLA)
Yin, Liusong…[et al.]. The Role of Aggregates of Therapeutic Protein Products in Immunogenicity: An Evaluation by Mathematical Modeling. Journal of Immunology Research No. 2015 (2015), pp.1-14.
https://search.emarefa.net/detail/BIM-1068468
American Medical Association (AMA)
Yin, Liusong& Chen, Xiaoying& Tiwari, Abhinav& Vicini, Paolo& Hickling, Timothy P.. The Role of Aggregates of Therapeutic Protein Products in Immunogenicity: An Evaluation by Mathematical Modeling. Journal of Immunology Research. 2015. Vol. 2015, no. 2015, pp.1-14.
https://search.emarefa.net/detail/BIM-1068468
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1068468