Biospecimens and Primagraft Development

生物样本和 Primaraft 开发

• 批准号: 10005155
• 负责人: Jennifer R Brown
• 金额: $ 31.64万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005155
• 关键词: 3-Dimensional; Biologic Characteristic; Biology; Bone Marrow; Cell Line; Cells; Clinical; Clinical Research; Clinical Trials; Communities; DNA; Dana-Farber Cancer Institute; Data; Development; Disease; Disease remission; Dissection; Doctor of Philosophy; Drug Approval; Drug resistance; Enrollment; Ensure; FDA approved; Foundations; Freezing; Future; Genetic; Genome; Grant; Histologic; Human; Implant; In Vitro; Infrastructure; Injections; Investigation; Lesion; Leukemic Cell; Methylation; Mission; Modeling; Molecular; Mononuclear; Multicenter Studies; Multiple Myeloma; Mutate; Pathogenesis; Pathologist; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Phase; Plasma; Polymers; Prediction of Response to Therapy; Principal Investigator; RNA; Relapse; Research; Research Support; Resistance; Resources; Saliva; Sampling; Signal Transduction; Somatic Mutation; System; Tail; Testing; Therapeutic Clinical Trial; Time; Tissue Banks; Tissues; Transgenic Organisms; Translating; Translational Research; Translations; Tumor Bank; Veins; Work; ZAP-70 Gene; bone; caprolactone; clinical development; experience; experimental study; follow-up; human model; humanized mouse; improved; in vivo; in vivo Model; inhibitor/antagonist; innovation; lymph nodes; mimetics; mouse model; mutational status; novel; novel marker; peripheral blood; phenome; pre-clinical; programs; prospective; response; scaffold; therapeutic target; tissue resource; tool; translational scientist; treatment trial; tumor

Project Summary This core will provide a seamless translational infrastructure to support the research on CLL tissues planned in this application. This will include the provision of fresh or frozen primary CLL samples (peripheral blood, bone marrow and lymph node) for all in vitro experiments, with full clinical annotation and follow-up, from among the over 1200 patients already enrolled in the DFCI CLL tissue bank as well as newly enrolled patients. The core includes extensive serial sampling from many CLL patients treated with novel agents, and will focus particularly on the acquisition of progression and relapsed samples during this grant period. This core also includes an effort to develop the capability of using primary CLL cells to generate in vivo primagraft models. These models are a significant and increasingly appreciated tool for the analysis of newly identified genetic lesions, associated signaling and survival pathways, rational therapeutic targets and mechanisms of drug resistance. CLL cells or isogenic cell lines will be delivered by tail vein injection or directly implanted within the coated scaffolds. CLL cells delivered to the scaffolds are expected to engraft within this “humanized mouse” system which is meant to simulate vital human-human heterotypic interactions between CLL and BM cells. These primagraft models could then be used to characterize biology and assess response to therapy of the CLLs. This core ultimately also readily provides the opportunity for translation to clinical research trials in humans, as our clinical DFCI CLL program consists of recognized leaders in managing all phases of clinical research trials as well as multicenter studies.

项目摘要 该核心将提供无缝的翻译基础架构，以支持CLL组织的研究 在此应用程序中计划。这将包括提供新鲜或冷冻的主要CLL样品 （外周血，骨髓和淋巴结）用于所有体外实验，并具有完整的临床注释 和后续行动，从已经入学的1200多名患者中 作为新入学的患者。核心包括来自许多CLL患者的大量连续采样 用新型药物处理，并将特别关注获取进展并传达 在此赠款期间样本。该核心还包括开发使用能力的努力 主要的CLL细胞生成体内Primagraft模型。这些模型很重要， 越来越多的工具用于分析新鉴定的遗传病变，相关信号 以及生存途径，耐药性的理性治疗靶标和机制。 Cll细胞或 等生细胞系将通过尾静脉注射或直接植入涂层的支架中。 预计将传递到脚手架的CLL单元将在此“人源化小鼠”系统中植入 这是为了模拟CLL和BM细胞之间重要的人类人类异型相互作用。 然后可以使用这些Primagraft模型来表征生物学和评估对治疗的反应 Clls。这个核心最终也很容易地为临床研究提供了翻译的机会 人类的试验，因为我们的临床DFCI CLL计划由公认的领导者组成 临床研究试验的阶段以及多中心研究。