A method to induce hen egg lysozyme-specific humoral immune tolerance in mice by pre-exposition with the protein's oligomers.
A method to induce hen egg lysozyme-specific humoral immune tolerance in mice by pre-exposition with the protein's oligomers.
复制标题
一种通过预先暴露蛋白质低聚物来诱导小鼠鸡蛋溶菌酶特异性体液免疫耐受的方法。
DOI：
10.1016/j.bbrep.2019.100679
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Ueda T.
中科院分区：
文献类型：
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作者：
Ohkuri T;Yuge N;Sato K;Ueda T.
在用蛋白质治疗剂（例如单克隆抗体）治疗期间，抗药抗体的发展是现代药理学的严重副作用。随着治疗性蛋白质的数量和暴露量的增加，产生抗药抗体。在这种情况下，较低的免疫原性反应可以减少这些有害作用。已知抗原的生物物理表征，即大小、化学组成、物理形式和可降解性，会影响免疫应答的结果。在这里，使用化学修饰，我们已经准备了鸡蛋溶菌酶（HEL），3- 5聚体，作为一个典型的抗原在免疫学和评估的效力作为耐受原在HEL-specific抗体反应的寡聚体。我们的结果清楚地表明，无论交联模式如何，将HEL-寡聚体预暴露于小鼠中都有效地抑制了HEL-特异性IgG应答。因此，寡聚化是一种诱导蛋白质致耐受性的方法，并可能成为控制不需要的抗蛋白药物抗体产生的有希望的策略。
During treatment with protein therapeutics, such as monoclonal antibodies, the development of anti-drug antibodies is a serious side-effect of modern pharmacology. Anti-drug antibodies are produced as the number and exposure to therapeutic proteins increase. In this context, less immunogenic responses could diminish these noxious effects. Biophysical characterization of antigens, that is size, chemical composition, physical form, and degrability, are known to influence the outcome of immune responses. Here, using chemical modification, we have prepared oligomers of hen egg lysozyme (HEL), 3- to 5-mer, as a typical antigen in immunology and evaluated the efficacy as a tolerogen in HEL-specific antibody responses. Our results clearly demonstrated that pre-exposed the HEL-oligomers into mice effectively suppressed HEL-specific IgG responses regardless of the cross-linking mode. Therefore, the oligomerization is a method to induce tolerogenicity of proteins and may emerge as a promising strategy to control the production of undesirable anti-protein drug antibodies.