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检测人血清中预先存在的抗聚乙二醇和聚乙二醇化脂质体的抗体。

Detection of Pre-Existing Antibodies to Polyethylene Glycol and PEGylated Liposomes in Human Serum.

机构信息

Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

出版信息

Methods Mol Biol. 2024;2789:185-192. doi: 10.1007/978-1-0716-3786-9_19.

DOI:10.1007/978-1-0716-3786-9_19
PMID:38507004
Abstract

Polyethylene glycol, or PEG, is common in consumer products, over-the-counter medications, food, and pharmaceutical products. Concerns about PEG immunogenicity and the subsequent negative impact of pre-existing and product-induced antibodies often shadow the benefits of using PEG in nanotechnology-based products. Such anti-PEG antibodies contribute to the accelerated blood clearance of PEGylated nanomedicines and result in premature drug release and antibody-mediated toxicities. Recent data demonstrated that using PEG in COVID-19 lipid nanoparticle-mRNA vaccines is associated with an induction of anti-PEG antibodies in healthy individuals, further contributing to the development or boosting of pre-existing antibodies and increasing the risks of antibody-mediated toxicities to other products containing PEG. Therefore, monitoring the levels of pre-existing and product-induced anti-PEG antibodies provides mechanistic insights for pharmacology, toxicology, and immunological studies of PEGylated drug products.

摘要

聚乙二醇(PEG)在消费品、非处方药、食品和药品中很常见。PEG 的免疫原性以及由此产生的预存抗体和产品诱导抗体的负面影响,常常使人们忽视了 PEG 在基于纳米技术的产品中的应用优势。这些抗 PEG 抗体导致 PEG 化纳米药物的血液清除加速,导致药物提前释放和抗体介导的毒性。最近的数据表明,在 COVID-19 脂质纳米颗粒-mRNA 疫苗中使用 PEG 会导致健康个体产生抗 PEG 抗体,进一步促进预存抗体的产生或增强,并增加其他含有 PEG 的产品发生抗体介导毒性的风险。因此,监测预存和产品诱导的抗 PEG 抗体水平,为 PEG 化药物产品的药理学、毒理学和免疫学研究提供了机制见解。

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本文引用的文献

1
Insights into the Structure of Comirnaty Covid-19 Vaccine: A Theory on Soft, Partially Bilayer-Covered Nanoparticles with Hydrogen Bond-Stabilized mRNA-Lipid Complexes.Comirnaty 新冠疫苗结构解析:带氢键稳定的 mRNA-脂质复合物的软、部分双层覆盖纳米颗粒的理论。
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Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions.辉瑞BNT162b2诱导的速发型疫苗超敏反应中的过敏毒素补体5a
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Anti-PEG IgM production induced by PEGylated liposomes as a function of administration route.
聚乙二醇化脂质体给药途径与抗聚乙二醇 IgM 产生的关系。
J Control Release. 2023 Aug;360:285-292. doi: 10.1016/j.jconrel.2023.06.027. Epub 2023 Jun 29.
4
Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination.评估抗聚乙二醇抗体与 mRNA COVID-19 疫苗接种后过敏反应的关系。
Vaccine. 2023 Jun 23;41(28):4183-4189. doi: 10.1016/j.vaccine.2023.05.029. Epub 2023 May 16.
5
Noncovalent PEGylation of protein and peptide therapeutics.蛋白质和肽类治疗药物的非共价聚乙二醇化
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2023 Sep-Oct;15(5):e1897. doi: 10.1002/wnan.1897. Epub 2023 May 3.
6
Antibodies against Poly(ethylene glycol) Activate Innate Immune Cells and Induce Hypersensitivity Reactions to PEGylated Nanomedicines.抗聚乙二醇(PEG)抗体激活固有免疫细胞,并诱导对 PEG 化纳米药物的过敏反应。
ACS Nano. 2023 Mar 28;17(6):5757-5772. doi: 10.1021/acsnano.2c12193. Epub 2023 Mar 16.
7
Lipid nanoparticles for gene therapy in ocular diseases.用于眼部疾病基因治疗的脂质纳米颗粒。
Daru. 2023 Jun;31(1):75-82. doi: 10.1007/s40199-023-00455-1. Epub 2023 Feb 15.
8
Clinical Impact of Antipolyethylene Glycol (PEG) Antibody in Hematological Patients Administered PEGylated-Granulocyte Colony-Stimulating Factor.聚乙二醇(PEG)抗体在接受 PEG 化粒细胞集落刺激因子治疗的血液系统疾病患者中的临床影响。
Clin Pharmacol Drug Dev. 2023 Aug;12(8):826-831. doi: 10.1002/cpdd.1225. Epub 2023 Jan 28.
9
Accelerated clearance by antibodies against methoxy PEG depends on pegylation architecture.针对甲氧基聚乙二醇的抗体加速清除取决于聚乙二醇化结构。
J Control Release. 2023 Feb;354:354-367. doi: 10.1016/j.jconrel.2023.01.021. Epub 2023 Jan 17.
10
Investigation of anti-PEG antibody response to PEG-containing cosmetic products in mice.研究含有聚乙二醇的化妆品产品在小鼠体内引起的抗聚乙二醇抗体反应。
J Control Release. 2023 Feb;354:260-267. doi: 10.1016/j.jconrel.2023.01.012. Epub 2023 Jan 12.