3D HUMAN TUMOR CO-CULTURE SYSTEM FOR ACCURATE Prediction of Clinical Efficacy

3D 人类肿瘤共培养系统可准确预测临床疗效

• 批准号: 8744490
• 负责人: HAL CROSSWELL
• 金额: $ 29.47万
• 依托单位: KIYATEC, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2014-06-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8744490
• 关键词: Antineoplastic Agents; Benchmarking; Biomedical Engineering; Breast; Breast Cancer Cell; Cancer cell line; Cell Line; Clinical; Clinical Trials; Coculture Techniques; Cues; Decision Making; Epithelial; Epithelial Cells; Evaluation; Failure; Hormonal; Human; In Situ; Longevity; Malignant - descriptor; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary gland; Modeling; Monitor; Morphology; Non-Malignant; Patients; Performance; Perfusion; Sampling; System; Testing; Therapeutic; Time; Tissue Model; anti-cancer therapeutic; clinical decision-making; clinical efficacy; drug development; immortalized cell; improved; malignant breast neoplasm; neoplastic cell; response; tumor; tumor microenvironment

This proposal will establish patient-derived 3D co-cultured micro tumors that will be used both to screen anticancer therapeutic compounds in drug development, leading to fewer clinical trial failures because of earlier, more relevant results and to test patient-derived samples in real time for clinical decision making. Our initial strategy will be to establish a human relevant model of the breast cancer microenvironment which can be monitored and evaluated for response using non-destructive means. Initially, an existing bioengineered 3D mammary gland tissue model¿s longevity, response to hormonal cues, and analytical evaluation improved through incorporation into a commercially available 3D co-culture perfusion system that permits non-destructive in situ monitoring. We will then characterize the effects of the diseased state (cancer) within the model by replacing the primary mammary epithelial cells with an immortalized, transformed breast cancer cell line using non-destructive analysis. Then, we will replace the immortalized cell lines with patient-derived primary breast epithelial tumor cells and treat with approved cancer drugs known to have clinical activity, in order to establish a benchmarked performance and proof of concept of the predictive power of the primary human 3D Co-cultures for drug development and real time therapeutic decision making.

该提案将建立源自患者的 3D 共培养微肿瘤，用于筛查 药物开发中的抗癌治疗化合物，导致临床试验失败的情况减少 更早、更相关的结果，并实时测试源自患者的样本以进行临床决策。 我们的初步策略是建立一个与人类相关的乳腺癌微环境模型， 可以使用非破坏性手段来监测和评估响应。最初，现有的 生物工程 3D 乳腺组织模型的寿命、对激素线索的反应以及分析 通过纳入市售 3D 共培养灌注系统改进了评估 允许无损现场监测。然后我们将描述患病状态的影响 （癌症）在模型中通过用永生化的、 使用非破坏性分析转化乳腺癌细胞系。然后，我们将替换不朽的 细胞系与患者来源的原发性乳腺上皮肿瘤细胞并用批准的癌症药物治疗 已知具有临床活性，以便建立基准性能和概念证明 主要人类 3D 共培养物对药物开发和实时治疗的预测能力 决策。