NSERC Strategic Network for the production of single-type glycoform monoclonal antibodies (Mabnet)

NSERC 用于生产单型糖型单克隆抗体的战略网络 (Mabnet)

• 批准号: 380070-2008
• 负责人: Butler, Michael
• 金额: $ 75.88万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Strategic Network Grants Program
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=484646
• 关键词: NSERC; Strategic; Network; production; single

with an estimated annual growth of 14% up to 2012, based on the most recent economic analysis . Since 1996 there have been 20 approvals for Mabs to be used as therapeutics. Six of these are blockbusters with annual sales in excess of a billon dollars per year. This proposal addresses the desirability of modifying and controlling the production of Mabs so that they have defined structures that maximize their potential for clinical use. The glycan structure attached to the Mab protein is variable but it has been shown that this component is extremely important for biological function. The proposed Mab network (MabNet) aims to produce Mabs with single or limited structural glycan variation. This will be performed by a combination of bioanalyticals, molecular biology, biochemical engineering, molecular re-construction and downstream processing and organized into specific Theme areas. The overall aim will be to develop a consistent method for the production of large quantities of single glycoform Mabs. There are several model Mabs that will be developed in the network. The lead candidate is a chimeric antibody (llama/human) which binds to human epidermal growth factor (hEGF). This has been shown to have good tumour targeting properties and a high level of penetration of solid tumours because of its small molecular size, The novel methods developed in the network will allow the full therapeutic potential of such Mabs to be realized.

根据最新的经济分析，预计到 2012 年年增长率为 14%。自 1996 年以来，已有 20 个单克隆抗体被批准用作治疗药物。其中有六部是年销售额超过十亿美元的大片。该提案解决了修改和控制单克隆抗体生产的需求，以便它们具有明确的结构，最大限度地发挥其临床应用的潜力。 Mab 蛋白上附着的聚糖结构是可变的，但已表明该成分对于生物功能极其重要。所提出的 Mab 网络 (MabNet) 旨在生产具有单一或有限结构聚糖变异的 Mab。这将通过生物分析、分子生物学、生化工程、分子重建和下游加工的结合来进行，并组织成特定的主题领域。总体目标是开发一种一致的方法来生产大量单糖型单克隆抗体。网络中将开发多种单克隆抗体模型。主要候选者是与人表皮生长因子（hEGF）结合的嵌合抗体（美洲驼/人）。由于其分子尺寸小，已被证明具有良好的肿瘤靶向特性和对实体瘤的高水平渗透。网络中开发的新方法将使此类单克隆抗体的全部治疗潜力得以实现。