Engineering therapeutic antibodies for patient safety: tackling the immunogenicity problem

Abstract Established monoclonal antibodies (mAbs) allow treatment of cancers, autoimmune diseases and other severe illnesses. Side effects either arise due to interaction with the target protein and its biology or result from of the patient’s immune system reacting to the foreign protein. This immun...

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Bibliographic Details
Published in:Protein engineering, design and selection design and selection, 2020-09, Vol.33
Main Authors: Ulitzka, Michael, Carrara, Stefania, Grzeschik, Julius, Kornmann, Henri, Hock, Björn, Kolmar, Harald
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal - genetics
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - therapeutic use
Epitopes, T-Lymphocyte - genetics
Epitopes, T-Lymphocyte - immunology
Humans
Protein Engineering
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Summary:Abstract Established monoclonal antibodies (mAbs) allow treatment of cancers, autoimmune diseases and other severe illnesses. Side effects either arise due to interaction with the target protein and its biology or result from of the patient’s immune system reacting to the foreign protein. This immunogenic reaction against therapeutic antibodies is dependent on various factors. The presence of non-human sequences can trigger immune responses as well as chemical and post-translational modifications of the antibody. However, even fully human antibodies can induce immune response through T cell epitopes or aggregates. In this review, we briefly describe, how therapeutic antibodies can interact with the patient’s immune system and summarize recent advancements in protein engineering and in silico methods to reduce immunogenicity of therapeutic monoclonal antibodies.
ISSN:1741-0126
1741-0134
DOI:10.1093/protein/gzaa025