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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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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
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author Bheemareddy, Bala Reddy
Reddy, Prakash Narayana
Vemparala, Kranthi
Dirisala, Vijaya R.
author_facet Bheemareddy, Bala Reddy
Reddy, Prakash Narayana
Vemparala, Kranthi
Dirisala, Vijaya R.
author_sort Bheemareddy, Bala Reddy
collection PubMed
description 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.
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spelling pubmed-95325032022-10-20 Enhancement of effector functions of anti-CD20 monoclonal antibody by increased afucosylation in CHO cell line through cell culture medium optimization Bheemareddy, Bala Reddy Reddy, Prakash Narayana Vemparala, Kranthi Dirisala, Vijaya R. J Genet Eng Biotechnol Research 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. Springer Berlin Heidelberg 2022-10-04 /pmc/articles/PMC9532503/ /pubmed/36194313 http://dx.doi.org/10.1186/s43141-022-00421-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Bheemareddy, Bala Reddy
Reddy, Prakash Narayana
Vemparala, Kranthi
Dirisala, Vijaya R.
Enhancement of effector functions of anti-CD20 monoclonal antibody by increased afucosylation in CHO cell line through cell culture medium optimization
title Enhancement of effector functions of anti-CD20 monoclonal antibody by increased afucosylation in CHO cell line through cell culture medium optimization
title_full Enhancement of effector functions of anti-CD20 monoclonal antibody by increased afucosylation in CHO cell line through cell culture medium optimization
title_fullStr Enhancement of effector functions of anti-CD20 monoclonal antibody by increased afucosylation in CHO cell line through cell culture medium optimization
title_full_unstemmed Enhancement of effector functions of anti-CD20 monoclonal antibody by increased afucosylation in CHO cell line through cell culture medium optimization
title_short Enhancement of effector functions of anti-CD20 monoclonal antibody by increased afucosylation in CHO cell line through cell culture medium optimization
title_sort enhancement of effector functions of anti-cd20 monoclonal antibody by increased afucosylation in cho cell line through cell culture medium optimization
topic Research
url 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
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