New High Throughput Anti-Tumor Drug Screening System

描述（由申请人提供）：这个SBIR项目专注于开发、验证和商业化一种先进的高通量抗肿瘤药物筛选平台（HTS），该平台采用了一种新的3D HuBioGEM检测技术。临床前药物筛选通常使用生化和基于细胞的分析系统进行。近年来，利用微载体、pHEMA- coating、凝胶层和悬垂滴等技术开发了更多相关的三维球体模型。虽然有用，但它们需要复杂的区域性协议，提供不需要的端点和/或对自动化应用程序效率不高。我们通过独特的顺磁颗粒（GEM），配制获得专利的HuBiogel（人类生物基质），创造了一种新颖的HuBioGEM培养体系。采用三维磁性生物凝胶和384阵列培养策略，我们建议开发一个强大的人类微肿瘤检测平台，用于药物疗效分析。I)使用HuBioGEM、NCI细胞系和定制阵列工具建立3D肿瘤生产、培养和分析方案；ii)证明HTS检测系统在评估许多已知药物的抗肿瘤活性方面的实用性。我们的综合方法将允许自动处理、成像和功能分析。将新的三维肿瘤系统与现有的球体模型进行比较，以确认其实际优势。我们相信这个3D肿瘤生物学平台将允许对临床前候选药物进行稳健和准确的预测，从而加速药物发现和开发计划。商业重要性和意义：目前市场上没有令人满意的HTS检测系统，该系统利用了全人体3D细胞培养技术。新的384孔肿瘤生物测定将用于自动化成像，功能，蛋白质组学和基因组分析平台。HuBioGEM培养试剂盒和即用型临床前检测筛检的销售将具有重要的全球市场。

DESCRIPTION (provided by applicant): This SBIR project is focused to develop, validate and commercialize an advanced high-throughput anti- tumor drug screening platform (HTS) which employs a new 3D HuBioGEM assay technology. Preclinical drug screening is commonly performed using biochemical and cell-based assay systems. In recent years, more relevant 3D spheroid models have been developed using microcarrier, pHEMA- coating, gel-layer and hanging-drop techniques. Although useful, these require difficult culture protocols, provide undesirable endpoints and/or are not efficient for automated applications. We have created a novel HuBioGEM culture system by formulating patented HuBiogel (human biomatrix) with unique paramagnetic particles (GEM). Employing 3D magnetic-biogel and 384-array culture strategies, we propose to develop a robust human microtumor assay platform for drug efficacy profiling. Phase I technical goals are: i) Establish 3D tumor production, culture and analysis protocols using HuBioGEM, NCI cell lines and custom array tools; and ii) Demonstrate utility of HTS assay system for evaluating anti-tumor activity of many known drugs. Our integrated approach will allow automated handling, imaging and functional analysis. New 3D tumor system will be compared with current spheroid model to confirm its practical advantages. We are confident this 3D tumor biology platform will permit robust and accurate prediction of preclinical drug candidates and thus will accelerate drug discovery and development programs. Commercial Importance & Significance: No satisfactory HTS assay system currently exists in market which utilizes fully-human 3D cell culture technology. New 384-well tumor bioassay will be useful for automated imaging, functional, proteomic and genomic analysis platforms. Sales of HuBioGEM culture kits and Ready-use preclinical assay screens would have significant world-wide market.