Telomerase-Specific Adenoviral Imaging Systems for Detecting and Isolating CTCs

描述(申请人提供)：肿瘤向外周血中释放细胞，产生转移使其致死。循环肿瘤细胞(CTCs)在许多类型的癌症患者中都被检测到，即使是那些没有临床明显转移迹象的患者也是如此。由于CTCs可以通过微创方法获得，因此CTCs的检测和特征对于早期诊断、预后和治疗监测以及对导致转移的分子和细胞事件的了解至关重要。我们的目标是建立一种灵敏可靠的方法来检测和捕获所有肿瘤类型的CTC，无论其组织来源如何，在研究和临床环境中。我们推测，端粒酶选择性腺病毒可以特异性地标记癌细胞，为有效检测和分离CTC提供了一种简单的方法。我们的具体目标是(1)构建带有优化的hTERT启动子的复制型腺病毒载体，用于选择性标记存活的癌细胞；(2)构建并鉴定一种可调控的端粒酶选择性腺病毒，用于检测和分离存活的CTCs。

DESCRIPTION (provided by applicant): Tumors shed their cells into the peripheral blood, generating metastases that confer their lethality. Circulating tumor cells (CTCs) have been detected in patients of many types of cancers, even those with no signs of clinically overt metastases. Because CTCs are accessible using minimally invasive procedures, the detection and characterization of CTCs are pivotal for early diagnosis, prognosis, and treatment monitoring, as well as for understanding of the molecular and cellular events that lead to metastases. Our objective is to establish a sensitive and reliable method for detecting and capturing CTCs of all tumor types, regardless of their tissue origins, in research and clinical settings. We hypothesize that the telomerase-selective adenoviruses specifically label cancer cells and provide a simple method for efficient CTC detection and isolation. Our specific aims are (1) to generate replication-competent adenoviral vectors with optimized hTERT promoters for selective labeling of viable cancer cells; (2) to generate and characterize a tet-regulatable telomerase-selective adenovirus for the detection and isolation of viable CTCs.