IGF::OT::IGF SBIR PHASE II TOPIC 328: SYNVIVO-TUMOR: A PHYSIOLOGICAL 3D MODEL OF THE TUMOR MICROENVIRONMENT

IGF::OT::IGF SBIR 第二阶段主题 328：SYNVIVO-肿瘤：肿瘤微环境的生理 3D 模型

• 批准号: 9357185
• 负责人: BALABHASKAR PRABHAKARPANDIAN
• 金额: $ 149.99万
• 依托单位: CFD RESEARCH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-14 至 2018-09-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9357185
• 关键词: 3-Dimensional; Architecture; Biological Assay; Biotechnology; Blood Circulation; Cells; Clinical; Clinical Data; Diffusion; Endothelial Cells; Environment; Fibroblasts; Goals; Heterogeneity; Hydrogels; Immune; Industry; Microfluidic Microchips; Modeling; Neoplasm Metastasis; Nonprofit Organizations; Organ; Patients; Pharmacologic Substance; Phase; Physiological; Pre-Clinical Model; Preclinical Drug Evaluation; Protocols documentation; Research; Sampling; Small Business Innovation Research Grant; Therapeutic; Universities; cell growth; design; in vitro Model; in vivo; migration; neoplastic cell; novel; screening; three-dimensional modeling; treatment response; tumor; tumor microenvironment; tumor progression

The overall goal of this project is to develop and validate a novel assay for mimicking the tumor microenvironment. Our proposed assay will accurately model the tumor microenvironment encompassing (a) circulation in the vessels, (b) transport across vessel walls, and (c) tumors cultured in a 3-dimensional environment. In Phase I, we successfully demonstrated our platform, including multi-cellular culture and drug screening. Detailed characterization of tumor cell growth, viability, migration and invasiveness was performed. Drug screening studies were performed to model the therapeutic responses. Quantitative differences between the tumor microenvironment parameters were demonstrated. In Phase II, assay parameters will be optimized to capture in vivo conditions including diffusion gradients, heterogeneity, and multi-cellular architecture. Assays for tumor progression and metastasis for organ specific tumors will be developed. The in vitro model will be validated against in vivo studies as well as available clinical data. The platform will be demonstrated for patient-derived samples. A multi-disciplinary approach comprising of industry-academic clinical team with substantial expertise in all facets of the proposed study has been assembled for successful execution. The developed product will be commercialized to pharmaceutical/biotech companies, research labs, universities and non-profit organizations.

该项目的总体目标是开发和验证模仿肿瘤微环境的新颖测定法。我们提出的测定将准确地对肿瘤微环境进行建模（a）血管中的循环，（b）跨容器壁的运输，以及（c）在3维环境中培养的肿瘤。在第一阶段，我们成功地展示了我们的平台，包括多细胞培养和药物筛查。进行了肿瘤细胞生长，活力，迁移和侵入性的详细表征。进行药物筛查研究以建模治疗反应。证明了肿瘤微环境参数之间的定量差异。在第二阶段，将优化测定参数以捕获体内条件，包括扩散梯度，异质性和多细胞体系结构。将开发针对器官特异性肿瘤的肿瘤进展和转移的测定。体外模型将针对体内研究以及可用的临床数据进行验证。该平台将用于患者衍生的样品。一种由行业学术临床团队组成的多学科方法，在拟议的研究的所有方面都具有丰富的专业知识，以成功地执行。开发的产品将用于制药/生物技术公司，研究实验室，大学和非营利组织。