2020年9月1日
Pegfilgrastim (PEG-G-CSF) induces anti-polyethylene glycol (PEG) IgM via a T cell-dependent mechanism
Biological and Pharmaceutical Bulletin
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- 巻
- 43
- 号
- 9
- 開始ページ
- 1393
- 終了ページ
- 1397
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1248/bpb.b20-00345
Protein-based therapeutics are beginning to be widely used in various clinical settings. Conjugation of polyethylene glycol (PEGylation) to protein therapeutics improves their circulation half-lives in the body. However, we and other groups observed that the initial dose of some PEGylated protein-based therapeutics may induce anti-PEG antibodies (primarily immunoglobulin M (IgM)), resulting in the accelerated clearance of a second dose. The mechanism behind the induction of anti-PEG IgM by PEGylated protein-based therapeutics is still unclear. In this study, we found that Pegfilgrastim (PEG-G-CSF, the PEGylated form of the recombinant human granulocyte colony-stimulating factor) induced anti-PEG IgM in mice when administered via either intravenous or subcutaneous administration. However, the anti-PEG IgM induction is diminished both in athymic nude mice lacking T cells and in splenectomized mice. In addition, anti-PEG IgM production was significantly diminished in the cyclophosphamide-treated mice depleted of B-cells. These results indicate that anti-PEG IgM production by Pegfilgrastim occurs in spleen in a T cell-dependent manner, which differs from anti-PEG IgM induced by PEGylated liposomes. However, B cells, both marginal zone and follicular, are essential for anti-PEG IgM production in both PEGylated preparations.
- リンク情報
- ID情報
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- DOI : 10.1248/bpb.b20-00345
- ISSN : 1347-5215
- ISSN : 0918-6158
- ORCIDのPut Code : 97728651
- SCOPUS ID : 85090260945