論文 - 詳細
| RRC ID | 36271 |
|---|---|
| 著者 | Tada M, Tatematsu K, Ishii-Watabe A, Harazono A, Takakura D, Hashii N, Sezutsu H, Kawasaki N. |
| タイトル | Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori). |
| ジャーナル | MAbs |
| Abstract |
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. |
| 巻・号 | 7(6) |
| ページ | 1138-50 |
| 公開日 | 2015-1-1 |
| DOI | 10.1080/19420862.2015.1078054 |
| PMID | 26261057 |
| PMC | PMC4966511 |
| MeSH | Animals Animals, Genetically Modified Antibodies, Monoclonal / genetics Antibodies, Monoclonal / immunology* Antibodies, Monoclonal / metabolism Antibody Specificity / immunology* Antibody-Dependent Cell Cytotoxicity / immunology Antigens, CD20 / immunology* Bombyx / genetics* CHO Cells Cell Line, Tumor Chromatography, Liquid Complement System Proteins / immunology Cricetinae Cricetulus Cytotoxicity, Immunologic / immunology Glycosylation Humans Mass Spectrometry Mice Recombinant Proteins / immunology* Recombinant Proteins / metabolism Rituximab / genetics Rituximab / immunology Rituximab / metabolism |
| IF | 4.634 |
| 引用数 | 21 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| カイコ | |