Design and engineering of deimmunized biotherapeutics

[Display omitted] •Immunogenicity as a risk factor for biotherapeutic agents.•Antibody epitope deletion as a strategy to evade antidrug antibodies.•T cell epitope deletion as a strategy to silence the antidrug immune response.•Multi-objective protein design algorithms to facilitate biotherapeutic de...

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Published inCurrent opinion in structural biology Vol. 39; pp. 79 - 88
Main Authors Griswold, Karl E, Bailey-Kellogg, Chris
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.08.2016
Subjects
Epitopes, T-Lymphocyte - immunology
Humans
Immunization
Protein Engineering - methods
Proteins - chemistry
Proteins - genetics
Proteins - immunology
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Abstract [Display omitted] •Immunogenicity as a risk factor for biotherapeutic agents.•Antibody epitope deletion as a strategy to evade antidrug antibodies.•T cell epitope deletion as a strategy to silence the antidrug immune response.•Multi-objective protein design algorithms to facilitate biotherapeutic deimmunization.•Highlights of recent experimental validation for deimmunized biotherapeutics. Therapeutic proteins are powerful next-generation drugs able to effectively treat diverse and devastating diseases, but the development and use of biotherapeutics entails unique challenges and risks. In particular, protein drugs are subject to immune surveillance in the human body, and ensuing antidrug immune responses can cause a wide range of problems including altered pharmacokinetics, loss of efficacy, and even life-threating complications. Here we review recent progress in technologies for engineering deimmunized biotherapeutics, placing particular emphasis on deletion of immunogenic antibody and T cell epitopes via experimentally or computationally guided mutagenesis.
AbstractList Therapeutic proteins are powerful next-generation drugs able to effectively treat diverse and devastating diseases, but the development and use of biotherapeutics entails unique challenges and risks. In particular, protein drugs are subject to immune surveillance in the human body, and ensuing antidrug immune responses can cause a wide range of problems including altered pharmacokinetics, loss of efficacy, and even life-threating complications. Here we review recent progress in technologies for engineering deimmunized biotherapeutics, placing particular emphasis on deletion of immunogenic antibody and T cell epitopes via experimentally or computationally guided mutagenesis.Therapeutic proteins are powerful next-generation drugs able to effectively treat diverse and devastating diseases, but the development and use of biotherapeutics entails unique challenges and risks. In particular, protein drugs are subject to immune surveillance in the human body, and ensuing antidrug immune responses can cause a wide range of problems including altered pharmacokinetics, loss of efficacy, and even life-threating complications. Here we review recent progress in technologies for engineering deimmunized biotherapeutics, placing particular emphasis on deletion of immunogenic antibody and T cell epitopes via experimentally or computationally guided mutagenesis.
Therapeutic proteins are powerful next-generation drugs able to effectively treat diverse and devastating diseases, but the development and use of biotherapeutics entails unique challenges and risks. In particular, protein drugs are subject to immune surveillance in the human body, and ensuing antidrug immune responses can cause a wide range of problems including altered pharmacokinetics, loss of efficacy, and even life-threating complications. Here we review recent progress in technologies for engineering deimmunized biotherapeutics, placing particular emphasis on deletion of immunogenic antibody and T cell epitopes via experimentally or computationally guided mutagenesis.
[Display omitted] •Immunogenicity as a risk factor for biotherapeutic agents.•Antibody epitope deletion as a strategy to evade antidrug antibodies.•T cell epitope deletion as a strategy to silence the antidrug immune response.•Multi-objective protein design algorithms to facilitate biotherapeutic deimmunization.•Highlights of recent experimental validation for deimmunized biotherapeutics. Therapeutic proteins are powerful next-generation drugs able to effectively treat diverse and devastating diseases, but the development and use of biotherapeutics entails unique challenges and risks. In particular, protein drugs are subject to immune surveillance in the human body, and ensuing antidrug immune responses can cause a wide range of problems including altered pharmacokinetics, loss of efficacy, and even life-threating complications. Here we review recent progress in technologies for engineering deimmunized biotherapeutics, placing particular emphasis on deletion of immunogenic antibody and T cell epitopes via experimentally or computationally guided mutagenesis.
Author Bailey-Kellogg, Chris
Griswold, Karl E
AuthorAffiliation 1 Thayer School of Engineering, Dartmouth, Hanover, NH, United States
2 Stealth Biologics LLC, Lyme, NH, United States
3 Department of Computer Science, Dartmouth, Hanover, NH, United States
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/27322891$$D View this record in MEDLINE/PubMed
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Snippet [Display omitted] •Immunogenicity as a risk factor for biotherapeutic agents.•Antibody epitope deletion as a strategy to evade antidrug antibodies.•T cell...
Therapeutic proteins are powerful next-generation drugs able to effectively treat diverse and devastating diseases, but the development and use of...
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SubjectTerms Epitopes, T-Lymphocyte - immunology
Humans
Immunization
Protein Engineering - methods
Proteins - chemistry
Proteins - genetics
Proteins - immunology
Title Design and engineering of deimmunized biotherapeutics
URI https://dx.doi.org/10.1016/j.sbi.2016.06.003
https://www.ncbi.nlm.nih.gov/pubmed/27322891
https://www.proquest.com/docview/1826702719
https://pubmed.ncbi.nlm.nih.gov/PMC5067179
Volume 39
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