• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文会议>Annual Meeting of the Japanese Association for Animal Cell Technology >Non-fucosylated Therapeutic Antibodies: The Next Generation of Therapeutic Antibodies
【24h】

Non-fucosylated Therapeutic Antibodies: The Next Generation of Therapeutic Antibodies

机译：非岩氧化治疗抗体：下一代治疗抗体

获取原文
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Therapeutic antibody IgGl has two /V-linked oligosaccharide chains bound to the Fc region. The oligosaccharides are of the complex biantennary type, composed of a trimannosyl core structure with the presence or absence of core fucose, bisecting iV-acetylglucosamine (GlcNAc), galactose, and terminal sialic acid, which gives rise to structural heterogeneity. Both human serum IgG and therapeutic antibodies are well known to be heavily fucosulated. Recently, antibody-dependent cellular cytotoxicity (ADCC), a lytic attack on antibody-targeted cells, has been found to be one of the critical effector functions responsible for the clinical efficacy of therapeutic antibodies such as anti-CD20 IgGl rituximab (Rituxan~R) and anti-Her2/neu IgGl trastuzumab (Herceptin~R). ADCC is triggered upon the binding of lymphocyte receptors (Fc gamma Rs) to the antibody Fc region. The activity is dependent on the amount of fucose attached to the innermost GlcNAc of Af-linked Fc oligosaccharide via an alpha-l,6-linkage, and is dramatically enhanced by a reduction in fucose. Non-fucosylated therapeutic antibodies show more potent efficacy than their fucosylated counterparts both in vitro and in vivo [7-14], and are not likely to be immunogenic because their carbohydrate structures are a normal component of natural human serum IgG. Thus, the application of non-fucosylated antibodies is expected to be a powerful and elegant approach to the design of the next generation therapeutic antibodies with improved efficacy. In thisreview, we discuss the importance of the oligosaccharides attached to the Fc region of therapeutic antibodies, especially regarding the inhibitory effect of fucosylated therapeutic antibodies on the efficacy of non-fucosylated counterparts in one medicalagent. The impact of completely non-fucosylated therapeutic antibodies on therapeutic fields will be also discussed.
机译：治疗性抗体的IgG1具有结合于Fc区的两个/ V连接的寡糖链。寡糖是复合双触角型，具有核心岩藻糖的存在或不存在一个三甘露芯结构构成的，二等分N-二乙酰葡糖胺（GlcNAc的），半乳糖，和末端唾液酸，其产生的结构异质性。人类血清IgG和治疗性抗体是公知的是重fucosulated。近来，抗体依赖性细胞毒性（ADCC），对抗体靶向细胞裂解性发作，已经发现，负责临床疗效的治疗性抗体，例如抗CD20的IgG1利妥昔单抗（利妥昔单抗〜的R的临界效应子功能一个）和抗Her2 / neu的的IgG1单抗（赫赛汀〜R）。 ADCC是在淋巴细胞受体（的FcγRs）至抗体Fc区的结合触发的。的活性依赖于通过α-1，6-键连接至阿 - 连接的Fc寡糖的最里面的GlcNAc的岩藻糖的量，并且显着地由在岩藻糖的减少增强。非岩藻糖基的治疗性抗体显示更有效的效力比在体外和体内[7-14]的岩藻糖化的对应，并且不太可能，因为它们的碳水化合物结构是天然人血清IgG的法向分量是免疫原性的。因此，非岩藻糖基的抗体的应用预期是一个强大的和优雅的方法具有改善的功效的下一代治疗性抗体的设计。在thisreview，对安装于治疗性抗体的Fc区的寡糖的重要性，特别是关于岩藻糖化的治疗性抗体的非岩藻糖化同行的功效在一个medicalagent的抑制作用。完全无岩藻糖基的治疗性抗体的治疗性字段的影响将被讨论。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号