期刊名称：Computational and Structural Biotechnology Journal
印刷版ISSN：2001-0370
出版年度：2021
卷号：19
页码：315-329
DOI：10.1016/j.csbj.2020.12.024
出版社：Computational and Structural Biotechnology Journal
摘要：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.
关键词：Protein therapeutic ; Immunogenicity ; Anti-drug-antibody ; T cell epitope ; B cell epitope ; ABR Antigen-binding region ; ADA Anti-drug antibody ; ANN Artificial neural network ; APC Antigen-presenting cell ; Bab Binding antibody ; BCR B cell receptor ; CDR Complementarity determining region ; CRISPR Clustered regularly interspaced short palindromic repeats ; DC Dendritic cell ; ELP Elastin-like polypeptide ; EPO Erythropoietin ; ER Endoplasmatic reticulum ; GLK Gelatin-like protein ; HAP Homo-amino-acid polymer ; HLA Human leukocyte antigen ; HMM Hidden Markov model ; Ig Immunoglobulin ; IL Interleukin ; LPS Lipopolysaccharide ; MHC Major histocompatibility complex ; Nab Neutralizing antibody ; NMR Nuclear magnetic resonance ; PAMP Pathogen-associated molecular pattern ; PAS Polypeptide composed of proline; alanine; and/or serine ; PBMC Peripheral blood mononuclear cell ; PD Pharmacodynamics ; PEG Polyethylene glycol ; PK Pharmacokinetics ; PRR Pattern recognition receptor ; PSA Sialic acid polymers ; RNN Recurrent artificial neural network ; SVM Support vector machine ; TAP Transporter associated with antigen processing ; TCR T cell receptor ; TLR Toll-like receptor ; XTEN “Xtended” recombinant polypeptide
