Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity
| Autor: | Svetlana Abbasova, Sergey A. Ivanov, Maxim Smolov, Vladimir Simonov, Dmitry Poteryaev, Aleksandr Piskunov |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Glycosylation medicine.drug_class Bioengineering CHO Cells Monoclonal antibody Applied Microbiology and Biotechnology Subclass 03 medical and health sciences chemistry.chemical_compound Cricetulus 0302 clinical medicine Antigen medicine Animals Humans 030212 general & internal medicine Biosimilar Pharmaceuticals Pharmacology Antibody-dependent cell-mediated cytotoxicity General Immunology and Microbiology biology Effector Receptors IgG Antibody-Dependent Cell Cytotoxicity General Medicine Trastuzumab Cell biology 030104 developmental biology chemistry Cell culture Immunoglobulin G biology.protein Antibody Biotechnology |
| Zdroj: | Biologicals. 58:16-21 |
| ISSN: | 1045-1056 |
| DOI: | 10.1016/j.biologicals.2019.01.002 |
| Popis: | Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market. IgG1 subclass is the most potent effector in Fc-related functions. The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process. Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar. We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC). |
| Databáze: | OpenAIRE |
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