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

该项目的总体目标是开发和验证一种模拟肿瘤微环境的新型检测方法。我们提出的分析将准确地模拟肿瘤微环境，包括(a)血管循环，(b)跨血管壁运输，以及(c)在三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选。详细描述肿瘤细胞的生长、活力、迁移和侵袭性。进行药物筛选研究以模拟治疗反应。证实了肿瘤微环境参数之间的定量差异。在第二阶段，将优化检测参数以捕获体内条件，包括扩散梯度、异质性和多细胞结构。针对器官特异性肿瘤的肿瘤进展和转移的检测将被开发出来。体外模型将根据体内研究和现有临床数据进行验证。该平台将用于患者来源的样本。一个由工业界和学术界临床团队组成的多学科方法，在拟议研究的各个方面都具有丰富的专业知识，已成功实施。开发的产品将商业化到制药/生物技术公司、研究实验室、大学和非营利组织。

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.