Deimmunization of protein therapeutics – Recent advances in experimental and computational epitope prediction and deletion
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Date
2021-01
Publication Type
Review Article
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yes
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Abstract
Biotherapeutics, and antimicrobial proteins in particular, are of increasing interest for human medicine. An important challenge in the development of such therapeutics is their potential immunogenicity, which can induce production of anti-drug-antibodies, resulting in altered pharmacokinetics, reduced efficacy, and potentially severe anaphylactic or hypersensitivity reactions. For this reason, the development and application of effective deimmunization methods for protein drugs is of utmost importance. Deimmunization may be achieved by unspecific shielding approaches, which include PEGylation, fusion to polypeptides (e.g., XTEN or PAS), reductive methylation, glycosylation, and polysialylation. Alternatively, the identification of epitopes for T cells or B cells and their subsequent deletion through site-directed mutagenesis represent promising deimmunization strategies and can be accomplished through either experimental or computational approaches. This review highlights the most recent advances and current challenges in the deimmunization of protein therapeutics, with a special focus on computational epitope prediction and deletion tools.
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published
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Journal / series
Volume
19
Pages / Article No.
315 - 329
Publisher
Research Network of Computational and Structural Biotechnology
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Edition / version
Methods
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Subject
Protein therapeutic; Immunogenicity; Anti-drug-antibody; T cell epitope; B cell epitope
Organisational unit
03651 - Loessner, Martin / Loessner, Martin