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...

• Type: Journal
• Year: 2010
• Where: BMCBI
• Authors: Andrew S. Parker, Wei Zheng, Karl E. Griswold, Chris Bailey-Kellogg
• Keywords: Anti-biotherapeutic Immune Response, BMCBI 2010, Protein, Therapeutic