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Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori)

In response to the successful use of monoclonal antibodies (mAbs) in the treatment of various diseases, systems for expressing recombinant mAbs using transgenic animals or plants have been widely developed. The silkworm (Bombyx mori) is a highly domesticated insect that has recently been used for th...

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Autores principales: Tada, Minoru, Tatematsu, Ken-Ichiro, Ishii-Watabe, Akiko, Harazono, Akira, Takakura, Daisuke, Hashii, Noritaka, Sezutsu, Hideki, Kawasaki, Nana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966511/
https://www.ncbi.nlm.nih.gov/pubmed/26261057
http://dx.doi.org/10.1080/19420862.2015.1078054
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author Tada, Minoru
Tatematsu, Ken-Ichiro
Ishii-Watabe, Akiko
Harazono, Akira
Takakura, Daisuke
Hashii, Noritaka
Sezutsu, Hideki
Kawasaki, Nana
author_facet Tada, Minoru
Tatematsu, Ken-Ichiro
Ishii-Watabe, Akiko
Harazono, Akira
Takakura, Daisuke
Hashii, Noritaka
Sezutsu, Hideki
Kawasaki, Nana
author_sort Tada, Minoru
collection PubMed
description In response to the successful use of monoclonal antibodies (mAbs) in the treatment of various diseases, systems for expressing recombinant mAbs using transgenic animals or plants have been widely developed. The silkworm (Bombyx mori) is a highly domesticated insect that has recently been used for the production of recombinant proteins. Because of their cost-effective breeding and relatively easy production scale-up, transgenic silkworms show great promise as a novel production system for mAbs. In this study, we established a transgenic silkworm stably expressing a human-mouse chimeric anti-CD20 mAb having the same amino acid sequence as rituximab, and compared its characteristics with rituximab produced by Chinese hamster ovary (CHO) cells (MabThera®). The anti-CD20 mAb produced in the transgenic silkworm showed a similar antigen-binding property, but stronger antibody-dependent cell-mediated cytotoxicity (ADCC) and weaker complement-dependent cytotoxicity (CDC) compared to MabThera. Post-translational modification analysis was performed by peptide mapping using liquid chromatography/mass spectrometry. There was a significant difference in the N-glycosylation profile between the CHO− and the silkworm-derived mAbs, but not in other post-translational modifications including oxidation and deamidation. The mass spectra of the N-glycosylated peptide revealed that the observed biological properties were attributable to the characteristic N-glycan structures of the anti-CD20 mAbs produced in the transgenic silkworms, i.e., the lack of the core-fucose and galactose at the non-reducing terminal. These results suggest that the transgenic silkworm may be a promising expression system for the tumor-targeting mAbs with higher ADCC activity.
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spelling pubmed-49665112016-08-24 Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori) Tada, Minoru Tatematsu, Ken-Ichiro Ishii-Watabe, Akiko Harazono, Akira Takakura, Daisuke Hashii, Noritaka Sezutsu, Hideki Kawasaki, Nana MAbs Report In response to the successful use of monoclonal antibodies (mAbs) in the treatment of various diseases, systems for expressing recombinant mAbs using transgenic animals or plants have been widely developed. The silkworm (Bombyx mori) is a highly domesticated insect that has recently been used for the production of recombinant proteins. Because of their cost-effective breeding and relatively easy production scale-up, transgenic silkworms show great promise as a novel production system for mAbs. In this study, we established a transgenic silkworm stably expressing a human-mouse chimeric anti-CD20 mAb having the same amino acid sequence as rituximab, and compared its characteristics with rituximab produced by Chinese hamster ovary (CHO) cells (MabThera®). The anti-CD20 mAb produced in the transgenic silkworm showed a similar antigen-binding property, but stronger antibody-dependent cell-mediated cytotoxicity (ADCC) and weaker complement-dependent cytotoxicity (CDC) compared to MabThera. Post-translational modification analysis was performed by peptide mapping using liquid chromatography/mass spectrometry. There was a significant difference in the N-glycosylation profile between the CHO− and the silkworm-derived mAbs, but not in other post-translational modifications including oxidation and deamidation. The mass spectra of the N-glycosylated peptide revealed that the observed biological properties were attributable to the characteristic N-glycan structures of the anti-CD20 mAbs produced in the transgenic silkworms, i.e., the lack of the core-fucose and galactose at the non-reducing terminal. These results suggest that the transgenic silkworm may be a promising expression system for the tumor-targeting mAbs with higher ADCC activity. Taylor & Francis 2015-08-11 /pmc/articles/PMC4966511/ /pubmed/26261057 http://dx.doi.org/10.1080/19420862.2015.1078054 Text en © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License http://creativecommons.org/licenses/by-nc/3.0/, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Report
Tada, Minoru
Tatematsu, Ken-Ichiro
Ishii-Watabe, Akiko
Harazono, Akira
Takakura, Daisuke
Hashii, Noritaka
Sezutsu, Hideki
Kawasaki, Nana
Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori)
title Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori)
title_full Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori)
title_fullStr Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori)
title_full_unstemmed Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori)
title_short Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori)
title_sort characterization of anti-cd20 monoclonal antibody produced by transgenic silkworms (bombyx mori)
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966511/
https://www.ncbi.nlm.nih.gov/pubmed/26261057
http://dx.doi.org/10.1080/19420862.2015.1078054
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