New High Throughput Anti-Tumor Drug Screening System

新型高通量抗肿瘤药物筛选系统

• 批准号: 8780336
• 负责人: RAJ K. SINGH
• 金额: $ 15.7万
• 依托单位: VIVO BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8780336
• 关键词: Adhesions; Antibodies; Antineoplastic Agents; Benchmarking; Biochemical; Biological Assay; Breast; Cell Culture Techniques; Cell Line; Cells; Collaborations; Colon; Culture Techniques; Custom; Data; Development; Devices; Dose; Drops; Evaluation; Exhibits; Functional Imaging; Future; Gel; Genomics; Goals; Growth; Human; Image; Image Analysis; Immune; Legal patent; Libraries; Lung; Magnetism; Marketing; Methods; Modeling; Outcome; Ovarian; Pharmaceutical Preparations; Phase; Physiological; Preclinical Drug Evaluation; Predictive Value; Production; Prostate; Proteomics; Protocols documentation; Reproducibility; Robotics; Sales; Scientist; Series; Small Business Innovation Research Grant; Staining method; Stains; System; Techniques; Technology; Time; Tumor Biology; Tumor Cell Line; Tumor-Derived; Validation; antitumor drug; base; calcein AM; drug candidate; drug development; drug discovery; drug efficacy; innovation; novel; particle; pre-clinical; programs; public health relevance; research and development; response; screening; success; tool; treatment effect; tumor

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.

描述（由申请人提供）：该SBIR项目专注于开发，验证和商业化高级高通量抗肿瘤药物筛查平台（HTS），该平台（HTS）采用了新的3D HubioGEM分析技术。临床前药物筛查通常是使用生化和基于细胞的测定系统进行的。近年来，使用微载体，Phema涂层，凝胶层和悬挂式滴滴技术开发了更相关的3D球体模型。尽管有用，但需要困难的文化协议，提供不良的终点和/或对自动化应用程序效率不高。我们通过用独特的顺磁性颗粒（GEM）制定了专利的Hubiogel（Human Biomatrix）来创建一种新型的Hubiogem培养系统。我们采用3D磁性双凝胶和384个阵列培养策略，我们建议开发一个强大的人类微肿块测定平台，以进行药物疗效分析。第一阶段的技术目标是：I）使用HubioGEM，NCI细胞系和自定义阵列工具建立3D肿瘤的生产，培养和分析方案； ii）证明了HTS测定系统用于评估许多已知药物的抗肿瘤活性的实用性。我们的集成方法将允许自动处理，成像和功能分析。新的3D肿瘤系统将与当前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药物的良好预测，因此将加速药物发现和开发计划。商业重要性和意义：目前在市场上没有令人满意的HTS分析系统，它利用了完全人类的3D细胞培养技术。新的384孔肿瘤生物测定将有助于自动成像，功能，蛋白质组学和基因组分析平台。 Hubiogem文化套件和现成的临床前测定屏幕的销售将具有重要的全球市场。