PRECLINICAL DRUG AND BIOLOGIC TESTING

临床前药物和生物测试

• 批准号: 8270603
• 负责人: Nino Keshelava
• 金额: $ 9.16万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8270603
• 关键词: Biological Assay; Biology; Cell Communication; Cell Line; Cells; Clinical Data; Clinical Investigator; Clinical Trials; Coculture Techniques; Collaborations; Combined Modality Therapy; Cultured Tumor Cells; Data Analyses; Disease; Drug Combinations; Generations; Human; IGF1R gene; Immunocompromised Host; In Vitro; Interleukin-6; Maximum Tolerated Dose; Mesenchymal; Modeling; Multi-Drug Resistance; Mus; Natural Killer Cells; Neuroblastoma; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase I Clinical Trials; Pre-Clinical Model; Research Personnel; STAT3 gene; Schedule; Testing; Tissues; Work; Xenograft Model; aurora-A kinase; cell bank; chemotherapeutic agent; combinatorial; cytotoxicity; design; high risk; in vivo; inhibitor/antagonist; instrument; lenalidomide; monocyte; neoplastic cell; neuroblastoma cell; novel therapeutics; pre-clinical; research clinical testing; research study; subcutaneous; tumor; tumor growth; tumor xenograft

The objective of the NANT Pre-Clinical Testing Lab is to facilitate the generation of hypothesis driven clinical trials within the NANT, and to provide guidance to NANT clinical investigators in prioritizing potential new therapeutics for phase I trials, and rational use of combinatorial therapy. The following Specific Aims will aid in achieving our objective: 1) Maintain a master cell bank of well-characterized human neuroblastoma cell lines. 2) Maintain DIMSCAN instrument in working order for use for experiments dealing with chemotherapeutic agents and IL-6, soluble IL-6, anti-IL-6 mAb CNTO 328, the STAT3 inhibitor stattic (Project 1), NK cells, anti-IGF1R mAb (Project 2), PI3K inhibitors, Aurora Kinase A type I and II inhibitors (Project 3), and drugs and drug combinations suggested by NANT investigators (Project 4). 3) Develop a "microenvironment" model by co-culturing tumor cells with representative microenvironment cells (e.g., monocytes, mesenchymal cells) to test by DIMSCAN therapies targeting tumor cell - microenvironment cell interaction (e.g., anti-IL-6 mAb; lenalidomide) (collaboration with Projects 1 and 2). 4) Conduct in vitro cytotoxicity assays using DIMSCAN and provide assistance to project investigators in designing experiments, instructing in use of DIMSCAN and analyzing of data. 5) Assess anti-tumor activity of selected combinations using subcutaneous and disseminated disease xenograft models of multi-drug-resistant human neuroblastomas in immunocompromised mice by 1) determining maximal tolerated dose (MTD) of selected drug combinations; 2) assessing pharmacodynamic evidence of drug activity at the MTD in tumor xenograft tissue; 3) assessing the effect of the most active combinations on tumor growth delay and mouse survival.

NANT临床前试验实验室的目标是促进在NANT内进行假设驱动的临床试验，并为NANT临床研究人员提供指导，优先考虑潜在的新治疗方法进行I期试验，并合理使用组合治疗。