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

根据最新的经济分析，预计到2012年的年增长率为14%。自1996年以来，已有20项单抗被批准用于治疗。其中六部是年销售额超过10亿美元的重磅炸弹。这项建议解决了修改和控制单抗生产的可取性，以使它们具有最大限度地发挥其临床应用潜力的结构。单抗蛋白上的糖链结构是多种多样的，但已证明这一成分对生物学功能极其重要。建议的单抗网络(MabNet)旨在生产具有单一或有限结构糖链变异的单抗。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相结合的方式进行，并组织成特定的主题领域。总体目标将是开发一种生产大量单糖型单抗的一致方法。将在该网络中开发几个模型单抗。领先的候选是一种与人表皮生长因子(HEGF)结合的嵌合抗体(骆驼/人)。这已被证明具有良好的肿瘤靶向性和高水平的实体肿瘤穿透，因为它的分子尺寸小，在网络中开发的新方法将使这种单抗的全部治疗潜力得以实现。

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.