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Enhancement of effector functions of anti-CD20 monoclonal antibody by increased afucosylation in CHO cell line through cell culture medium optimization

BACKGROUND: Recombinant therapeutic anti-CD20 monoclonal antibody (mAb) is used for the treatment of non-Hodgkin’s lymphoma, a common B cell lymphoma constituting 80% of all lymphomas. Anti-CD20 mAb contains an Fc-linked biantennary glycan. Although, anti-CD20 monoclonal antibodies are being increas...

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Detalles Bibliográficos
Autores principales: Bheemareddy, Bala Reddy, Reddy, Prakash Narayana, Vemparala, Kranthi, Dirisala, Vijaya R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532503/
https://www.ncbi.nlm.nih.gov/pubmed/36194313
http://dx.doi.org/10.1186/s43141-022-00421-5
Descripción
Sumario:BACKGROUND: Recombinant therapeutic anti-CD20 monoclonal antibody (mAb) is used for the treatment of non-Hodgkin’s lymphoma, a common B cell lymphoma constituting 80% of all lymphomas. Anti-CD20 mAb contains an Fc-linked biantennary glycan. Although, anti-CD20 monoclonal antibodies are being increasingly used for immunotherapy, their efficacy is limited in a section of patients with drug resistance to immunotherapy. There is a need to improve the efficacy by increasing the effector functions, such as the antibody-dependent cellular cytotoxicity (ADCC) activity of anti-CD20 monoclonal antibodies. RESULTS: We developed a simple and cost-effective approach to enhance ADCC effector activity in an in-house developed clone of anti-CD20 monoclonal antibody by increasing afucosylation in a new clone of Chinese Hamster Ovary (CHO) cells using 8X uridine, manganese, and galactose (UMG) to modulate the osmolality of the medium. The purified anti-CD20 monoclonal antibody from 8X UMG-containing medium showed a 2-fold increase in afucose content and 203% ADCC activity in comparison to control antibody. CONCLUSIONS: Our study reports enhanced ADCC activity by modulating afucosylation using osmolality by altering simple feed additives in the culture medium. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s43141-022-00421-5.