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

根据最新的经济分析，到2012年，估计年增长率为14%。自1996年以来，已经有20个单克隆抗体被批准用作治疗药物。其中六部是年销售额超过10亿美元的大片。该提案提出了修改和控制单克隆抗体生产的可取性，以便它们具有最大限度地发挥其临床应用潜力的定义结构。与Mab蛋白连接的聚糖结构是可变的，但已显示该组分对生物学功能极其重要。所提出的单克隆抗体网络（MabNet）旨在产生具有单一或有限结构聚糖变异的单克隆抗体。这将通过生物分析，分子生物学，生物化学工程，分子重建和下游加工的组合进行，并组织成特定的主题领域。总体目标是开发一种用于生产大量单糖型单克隆抗体的一致方法。有几个模型单克隆抗体，将在网络中开发。主要候选物是与人表皮生长因子（hEGF）结合的嵌合抗体（美洲驼/人）。这已被证明具有良好的肿瘤靶向特性和高水平的实体瘤渗透，因为它的小分子尺寸，在网络中开发的新方法将允许实现这种单克隆抗体的全部治疗潜力。

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.