2019 Fiscal Year Final Research Report
Rational design of poly(ethylene glycol) derivatives for reduction of antibody responses against poly(ethylene glycol)
| Project/Area Number |
17K01393
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
横山 昌幸 東京慈恵会医科大学, 医学部, 教授 (20220577)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | ポリエチレングリコール / 免疫原性 / 特異IgM抗体 |
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| Outline of Final Research Achievements |
Poly(ethylene glycol) is one of the most useful synthetic polymers for biopharmaceutics. As well as protein PEGylation, nano-sized drug carriers (nanomedicines) use PEG for surface coverages to escape bindings from serum proteins. As a result of PEGylation on the surfaces, PEGylated nanomedicines exhibit long blood circulation characteristics. However, IgM antibodies against PEG (anti-PEG IgM) have been found in PEGylated nanomedicine, such as PEG-liposome- and PEGylated micelle-injected animals. We have found that anti-PEG IgM does not bind to the PEG chain, but bind to PEG-conjugates. This unique characteristic of anti-PEG antibodies may be a key to suppress antibody responses against PEG, therefore, we synthesized a series of new PEG-triblock copolymer possessing polyanion between a PEG and a hydrophobic block to reduce anti-PEG Ab responses. Reduction of anti-PEG Ab responses have been observed in a polyanion-chain-length dependent manner.
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| Free Research Field |
高分子化学
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| Academic Significance and Societal Importance of the Research Achievements |
ポリエチレングリコール（PEG）は汎用性の高い高分子である。特に、医薬品としてのPEGはその水和効果によって、タンパク質やドラッグキャリアの血中半減期の向上やタンパク質の免疫原性の低減など、医薬品にとってのPEG化はゴールデンスタンダードであり、非常に有効な手段であることが知られている。しかしながら、近年、PEGに対する抗体（PEG特異抗体）が薬物キャリアによって産生されることが知られている。本研究は、PEGを用いながらPEGに対する特異抗体が抑制される新たなPEG分子を設計し、作製されたPEG分子を有する薬物キャリアが免疫原性を低減することを立証した。
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