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.

项目概要 该核心将提供无缝转化基础设施来支持 CLL 组织的研究 计划在此应用程序中。这将包括提供新鲜或冷冻的 CLL 初级样本 （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 以及来自 DFCI CLL 组织库的 1200 多名患者的后续跟踪 作为新入组的患者。核心包括来自许多 CLL 患者的广泛连续采样 用新药治疗，并将特别关注进展和复发的获得性 在此资助期内提供样品。该核心还包括努力开发使用 原代 CLL 细胞生成体内原代移植物模型。这些模型是重要且 用于分析新发现的遗传病变和相关信号传导的越来越受欢迎的工具 生存途径、合理治疗靶点和耐药机制。 CLL 细胞或 同基因细胞系将通过尾静脉注射输送或直接植入涂层支架内。 递送到支架上的 CLL 细胞预计将移植到这个“人源化小鼠”系统中 其目的是模拟 CLL 和 BM 细胞之间重要的人与人异型相互作用。 然后，这些原代移植物模型可用于表征生物学并评估对治疗的反应 CLL 的。该核心最终也很容易提供转化为临床研究的机会 人体试验，因为我们的临床 DFCI CLL 项目由管理所有疾病的公认领导者组成 临床研究试验以及多中心研究的各个阶段。