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项目的重点是开发、验证和商业化先进的高通量抗肿瘤药物筛选平台（HTS），该平台采用新的3D HuBioGEM检测技术。临床前药物筛选通常使用生物化学和基于细胞的测定系统进行。近年来，已经使用微载体、pHEMA涂层、凝胶层和悬滴技术开发了更相关的3D球体模型。虽然有用，但这些需要困难的培养方案，提供不期望的终点和/或对于自动化应用不是有效的。我们已经创建了一个新的HuBioGEM培养系统，通过制定专利HuBiogel（人类生物基质）与独特的顺磁性颗粒（GEM）。采用3D磁凝胶和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。第一阶段的技术目标是：i）使用HuBioGEM、NCI细胞系和定制阵列工具建立3D肿瘤产生、培养和分析方案;和ii）证明HTS测定系统用于评估许多已知药物的抗肿瘤活性的效用。我们的集成方法将允许自动化处理、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，以确认其实用优势。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：目前市场上还没有令人满意的HTS检测系统，其利用全人类3D细胞培养技术。新的384孔肿瘤生物测定将用于自动成像、功能、蛋白质组学和基因组学分析平台。HuBioGEM培养试剂盒和即用型临床前检测筛选的销售将具有重要的全球市场。