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Towards a novel 3D cell culture model to test the therapeutic efficacy of Affimers in the treatment of HER2 overexpressing breast cancer

建立新型 3D 细胞培养模型来测试 Affimers 在治疗 HER2 过表达乳腺癌中的疗效

基本信息

批准号：
2310402
负责人：
金额：
--
依托单位：
University of Leeds
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2310402
关键词：
Towards novel 3D cell culture

项目摘要

Breast cancer (BC) is the most commonly diagnosed cancer amongst women. Human epidermal receptor 2 (HER2) is overexpressed in 15-30 % of BC and is associated with poorer prognosis with comparison to the luminal subtypes. The monoclonal antibody (MAb) Trastuzumab is currently used for its treatment.Mouse models have and continue to be valuable models of BC, however, to address the 3 R's it is desirable to reduce, refine and replace their use in research. Here, a novel in vitro 3D culture model of HER2+ BC is being investigated. The HER2 overexpressing cell line BT-474 were cultured as spheroids in a matrix-free medium, epiFL. Spheroids show characteristics of a tumour such as a necrotic core and 3D structure so are more translational to the clinic than 2D culture models. Cells were then cultured in SeedEZ scaffolds. The scaffolds are hydrophilic consisting of glass fibers that allow spheroids to form in between them. SeedEZ were cultured with PerfusionPal to more closely mimic the environment of a tumour in vivo. Furthermore Affimers, an antibody replacement protein scaffold, that bind HER2 have been identified and their effects on inhibiting HER2+ cell growth will be studied. This is towards the creation of a fully humanised 3D model to test and compare the efficacy of Affimers in comparison to Trastuzumab in the treatment of HER2+ BC, potentially reducing the need for animals in preclinical drug testing.

乳腺癌（BC）是女性中最常见的癌症。人表皮受体2 （HER2）在15- 30%的BC中过表达，与管腔亚型相比，其预后较差。单克隆抗体（MAb）曲妥珠单抗目前用于其治疗。小鼠模型已经并将继续是有价值的BC模型，然而，为了解决3r问题，在研究中减少、改进和替代它们的使用是可取的。在这里，我们正在研究一种新的HER2+ BC体外3D培养模型。将HER2过表达细胞系BT-474在无基质的epiFL培养基中培养成球形。球体显示肿瘤的特征，如坏死的核心和三维结构，因此比二维培养模型更能转化为临床。然后在SeedEZ支架中培养细胞。支架是亲水的，由玻璃纤维组成，允许球体在它们之间形成。SeedEZ与PerfusionPal一起培养，以更接近地模拟体内肿瘤的环境。此外，已经鉴定出结合HER2的抗体替代蛋白支架Affimers，并将研究其抑制HER2+细胞生长的作用。这是为了创建一个完全人性化的3D模型，以测试和比较Affimers与曲妥珠单抗治疗HER2+ BC的疗效，潜在地减少临床前药物测试对动物的需求。