Development of a Human Intraepithelial Cancer Model

描述（申请人提供）：超过一半的人类癌症发生在 鳞状上皮为了加强药物发现，以治疗 鳞状细胞癌（SCC）和其他癌症，有必要有一个 重演肿瘤和正常上皮细胞的器官型体外模型 交互.艾伦-霍夫曼实验室最近开发了一种器官型 该模型允许在分层的人类鳞状细胞中评估肿瘤生长 上皮细胞该模型是遗传标记的人SCC细胞和 未标记的自发永生化的人角质形成细胞，称为NIKS细胞。 与目前的体外测定不同，该模型考虑了细胞因子的影响。 正常组织微环境对SCC生长和分化的影响 细胞另一个优势是该模型与其他上皮癌的相关性 (e.g.,宫颈、气管）以及与其他治疗方法结合的能力 (e.g.,手术、放射）。我们对这一建议的战略是验证和 在已知的和新的存在下优化器官型共培养物， 抗癌剂（例如，化疗药物、细胞抑制药物）和定量 它们通过监测基因标记的SCC对恶性细胞生长的影响 细胞在第一期工程完成前，我们计划发展一个 高通量、微升体积筛选形式来鉴定新的 使用基于NIKS的人NTM肿瘤测定法测定抗肿瘤剂。 拟定商业应用： 有效的杜尔格发现的关键是体外模型能够测试潜在的 在生理学相关背景下的抗癌剂。 Stratatech正在开发产品 使用基因标记的鳞状细胞癌的共培养系统 (SCC)在由我们的专有NIKS细胞系组成的器官型培养物中培养细胞。 该模型 该系统代表了筛选潜在药物或制剂的重大技术进步 用于治疗复层鳞状上皮细胞癌（例如，头颈部、口腔粘膜 子宫颈、气管）。

DESCRIPTION (PROVIDED BY APPLICANT): Over half of all human cancers occur in squamous epithelia. In order to enhance drug discovery for the treatment of squamous cell carcinoma (SCC) and other cancers, it is essential to have an organotypic in vitro model which recapitulates tumor and normal epithelial interactions. The Allen-Hoffmann laboratory recently developed an organotypic model that permits the assessment of tumor growth in stratified human squamous epithelia. The model is a co-culture of genetically marked human SCC cells and unmarked spontaneously immortalized human keratinocytes called NIKS cells. Unlike current in vitro assays, this model accounts for the influence of the normal tissue microenvironment (NTM) on the growth and differentiation of SCC cells. Another advantage is the model's relevance for other epithelial cancers (e.g., cervix, trachea) and its capacity for combination with other treatments (e.g., surgery, radiation). Our strategy for this proposal is to validate and optimize the organotypic co-cultures in the presence of known and novel anticancer agents (e.g., chemotherapeutics, cytostatic drugs) and quantify their effect on malignant cell growth by monitoring the genetically marked SCC cells. Pending completion of this Phase I work, we plan to develop a high-throughput, microliter-volume screening format to identify novel anti-tumor agents using the NIKS-based, human NTM tumor assay. PROPOSED COMMERCIAL APPLICATION: It is essential for effective durg discovery that in vitro models be able to test potential anticancer agents in a physiologically relevant context. Stratatech is developing products and services using a co-cultured system of genetically tagged squamous cell carcinoma (SCC) cells in an organotypic culture comprised of our propietary NIKS cell line. This model system represents a major technological advance for screening drugs or agents of potential use in treating cancers of the stratified squamous epithelia (e.g., head and neck, oral mucosa, cervix, trachea).