Protein deimmunization via structure-based design enables efficient epitope deletion at high mutational loads.

ABSTRACT: Anti-drug immune responses are a unique risk factor for biotherapeutics, and undesired immunogenicity can alter pharmacokinetics, compromise drug efficacy, and in some cases even threaten patient safety. To fully capitalize on the promise of biotherapeutics, more efficient and generally applicable protein deimmunization tools are needed. Mutagenic deletion of a protein's T cell epitopes is one powerful strategy to engineer immunotolerance, but deimmunizing mutations must maintain protein structure and function. Here, EpiSweep, a structure-based protein design and deimmunization algorithm, has been used to produce a panel of seven beta-lactamase drug candidates having 27-47% reductions in predicted epitope content. Despite bearing eight mutations each, all seven engineered enzymes maintaine

SUBMITTER: Salvat RS 

PROVIDER: S-EPMC4452428 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature