2025-03-05 九州大学
<関連情報>
- https://www.kyushu-u.ac.jp/ja/researches/view/1225
- https://www.kyushu-u.ac.jp/f/60856/25_0305_01.pdf
- https://www.sciencedirect.com/science/article/abs/pii/S0168365925001063
柔軟で特徴のないPEG鎖を捕捉するためにナイーブな抗PEG抗体が用いる戦略 The strategy used by naïve anti-PEG antibodies to capture flexible and featureless PEG chains
Yiwei Liu, Takahiro Mori, Yusei Ito, Kimiko Kuroki, Seiichiro Hayashi, Daisuke Kohda, Taro Shimizu, Tatsuhiro Ishida, Steve R. Roffler, Mika K. Kaneko, Yukinari Kato, Takao Arimori, Takamasa Teramoto, Kazuhiro Takemura, Kenta Ishibashi, Yoshiki Katayama, Katsumi Maenaka, Yoshimitsu Kakuta, Akio Kitao, Takeshi Mori
Journal of Controlled Release Available online: 10 February 2025
DOI:https://doi.org/10.1016/j.jconrel.2025.02.001
Graphical abstract
This study unveils mechanisms of PEG binding by naïve anti-PEG IgM—PEG chain sliding, terminal interaction, and tunnel-forming mutations—revealed through VDJ profiling, structural analysis, and simulations.
Abstract
Polyethylene glycol (PEG) is widely used as a standard stealth polymer, although the induction of anti-PEG antibodies and consequent effects have drawn attention in recent years. To date, several anti-PEG antibodies induced by PEG-modified proteins via the T cell-dependent (TD) pathway, in which affinity maturation occurs, have been reported. In contrast, structures of the naïve anti-PEG antibodies before affinity maturation have not been described in the literature. Here, to understand the details of the naïve anti-PEG antibodies capturing PEG, we studied a naïve anti-PEG antibody induced by a PEG-modified liposome in the absence of affinity maturation via the T cell-independent (TI) pathway. The mutation levels, structures as well as in vitro and in silico binding properties of TI and TD anti-PEG antibodies were compared. The TI anti-PEG antibody showed no mutation and a low binding affinity toward PEG, meanwhile, it allowed PEG chain sliding and weak interaction with the terminal group. Furthermore, the naïve anti-PEG antibodies may obtain high affinities by forming tunnel structures via minimal mutations. This research provides new insights into polymer–antibody interactions, which can facilitate the development of novel stealth polymers that can avoid antibody induction.
