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BMCBI
2010

Optimization algorithms for functional deimmunization of therapeutic proteins

13 years 3 months ago
Optimization algorithms for functional deimmunization of therapeutic proteins
Background: To develop protein therapeutics from exogenous sources, it is necessary to mitigate the risks of eliciting an anti-biotherapeutic immune response. A key aspect of the response is the recognition and surface display by antigen-presenting cells of epitopes, short peptide fragments derived from the foreign protein. Thus, developing minimal-epitope variants represents a powerful approach to deimmunizing protein therapeutics. Critically, mutations selected to reduce immunogenicity must not interfere with the protein's therapeutic activity. Results: This paper develops methods to improve the likelihood of simultaneously reducing the anti-biotherapeutic immune response while maintaining therapeutic activity. A dynamic programming approach identifies optimal and near-optimal sets of conservative point mutations to minimize the occurrence of predicted T-cell epitopes in a target protein. In contrast with existing methods, those described here integrate analysis of immunogenici...
Andrew S. Parker, Wei Zheng, Karl E. Griswold, Chr
Added 08 Dec 2010
Updated 08 Dec 2010
Type Journal
Year 2010
Where BMCBI
Authors Andrew S. Parker, Wei Zheng, Karl E. Griswold, Chris Bailey-Kellogg
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