Telomerase-Specific Adenoviral Imaging Systems for Detecting and Isolating CTCs

用于检测和分离 CTC 的端粒酶特异性腺病毒成像系统

• 批准号: 8245433
• 负责人: JIYUE ZHU
• 金额: $ 7.65万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8245433
• 关键词: Address; Adenoviruses; Affect; Antibodies; Antigens; CMV promoter; Cancer Patient; Cancer cell line; Catalytic Domain; Cell Adhesion Molecules; Cell surface; Cells; Clinical; Clinical Trials; Colorectal Cancer; Cytokeratin; DNA Tumor Viruses; Detection; Devices; Doxycycline; Early Diagnosis; Elements; Epithelial; Epithelial Cells; Evaluation; Event; FDA approved; Fibroblasts; Future; Gene Expression Regulation; Generations; Genes; Heterogeneity; Human; Image; Label; Lead; Magnetism; Malignant Neoplasms; Mesenchymal; Methods; Molecular; Monitor; Neoplasm Metastasis; Normal Cell; Patients; Principal Investigator; Procedures; Property; Recombinants; Reporting; Research; Research Personnel; Solid Neoplasm; Somatic Cell; Stem cells; System; TERT gene; Techniques; Technology; Telomerase; Testing; Tetanus Helper Peptide; Tissues; Training; Tumor Stem Cells; Viral; Work; base; cancer cell; cancer recurrence; cancer type; clinically relevant; expectation; metastatic colorectal; minimally invasive; neoplastic cell; novel; outcome forecast; peripheral blood; platform-independent; prognostic indicator; promoter; replication competent adenoviral vector; treatment response; tumor; vector

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. PUBLIC HEALTH RELEVANCE: Circulating tumor cells are clinically relevant for early detection of primary cancers, evaluation of treatment responses, and as a prognostic indicator on primary cancer recurrence and metastasis. In this application, we plan to develop a new generation of recombinant adenoviral imaging systems for detection and isolation of telomerase-positive circulating tumor cells.

描述（由申请人提供）：肿瘤将其细胞脱落到外周血中，产生转移，从而赋予其致命性。在许多类型的癌症患者中都检测到了循环肿瘤细胞（CTC），甚至是那些没有临床明显转移迹象的癌症患者。由于 CTC 可以通过微创手术获得，因此 CTC 的检测和表征对于早期诊断、预后和治疗监测以及了解导致转移的分子和细胞事件至关重要。我们的目标是建立一种灵敏可靠的方法，用于在研究和临床环境中检测和捕获所有肿瘤类型的 CTC，无论其组织来源如何。我们假设端粒酶选择性腺病毒特异性标记癌细胞，并为有效 CTC 检测和分离提供简单的方法。我们的具体目标是（1）生成具有复制能力的腺病毒载体，并具有优化的 hTERT 启动子，用于选择性标记活癌细胞； (2) 生成并表征 tet 可调节端粒酶选择性腺病毒，用于检测和分离活 CTC。 公共卫生相关性：循环肿瘤细胞在临床上与原发性癌症的早期检测、治疗反应的评估以及作为原发性癌症复发和转移的预后指标相关。在此应用中，我们计划开发新一代重组腺病毒成像系统，用于检测和分离端粒酶阳性循环肿瘤细胞。