Biospecimens and Patient-derived xenografts

生物样本和患者来源的异种移植物

基本信息

批准号：
10162305
负责人：
David Marc Weinstock
金额：
$ 13.77万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-07 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10162305
关键词：
Aftercare Biological Assay Biological Models Budgets Cancer Center Cell Culture Techniques Cell Line Cell Separation Cell model Cells Clinic Clinical Colon Carcinoma Colonic Neoplasms Complement Consent Cryopreservation DNA sequencing Data Devices Disease model Documentation Drug usage Ensure Epithelial Fresh Tissue Generations Genomic DNA Genomics Goals Grant Hematologic Neoplasms Histologic Human Human Cell Line Immunocompromised Host Immunodeficient Mouse Immunophenotyping In Vitro Informed Consent Infrastructure Institutional Review Boards Laboratories Leukemic Cell Malignant Neoplasms Malignant neoplasm of pancreas Medical Oncologist Methods Modeling Molecular Molecular Profiling Mus Oncology Organoids Pathologic Patient Care Patients Pharmaceutical Preparations Phenotype Plasma Population Preclinical Drug Evaluation Primary Neoplasm Protocols documentation Quality Control Research Research Infrastructure Research Personnel Research Project Grants Resources Sampling Serum Services Source Specimen Standardization Stromal Cells Techniques Therapeutic Tissue Model Tissue Sample Tissue Viability Tissues Translational Research Transplantation Tumor Tissue Work Xenograft procedure base biobank cancer genome cell preparation drug testing experience gastrointestinal genome-wide human tissue in vivo innovation interest leukemia model design neoplastic cell pancreatic cancer patients pancreatic neoplasm patient derived xenograft model pre-clinical pre-clinical assessment programs repository single cell analysis success targeted treatment therapy resistant tissue resource transcriptome tumor

项目摘要

Core 1 – Project Summary The overarching goal of Core 1 is to provide the infrastructure and professional expertise needed to bank primary leukemia, colon, and pancreatic cancer specimens, establish patient-derived xenograft (PDX), organoid, and cell models, and make these patient-derived resources available to all Program investigators, thereby facilitating the translational and laboratory-based research performed by CSBC investigators in Projects 1 and 2. Both projects will require access to patient samples and cells derived from PDX and organoid models. The core supports 3 functions: (1) cryopreservation and distribution of primary cells from patients with leukemia, colon, and pancreatic cancer, (2) establishment, characterization, and distribution of xenograft, organoid, and cell culture models of these diseases, and (3) isolation of cell populations from primary tumor samples and tissue models for single cell analysis. The functions of the core include documentation and tracking of informed consent, isolation and cryopreservation of viable tissue, plasma or serum, and genomic DNA from patient samples and distribution of samples to CSBC investigators. A large number of primary leukemia, colon and pancreatic tumor samples are currently available in our existing repositories for use by Project Investigators. Additional samples will be acquired from patients routinely evaluated in our gastrointestinal oncologic and hematologic malignancies clinics. In addition to distributing primary cells to program investigators, Core 1 will also maintain and distribute a bank of well characterized PDXs selected for passage in immunocompromised mice. Methods for engrafting leukemia cells and primary epithelial tumor tissues in immunodeficient mice are now well established, and we and others have successfully used PDX models for drug testing. Organoid culture approaches will be used to complement the PDX effort, and will provide an additional way of propagating and segregating patient-derived epithelial tumor cells and stromal cells. Core 1 will maintain a bank of PDX models and organoids and distribute to program investigators as needed. Core 1 will be jointly directed by Drs. William Hahn and Dr. David Weinstock. Dr. Hahn is a medical oncologist who directs the DFCI Center for Cancer Genome Discovery (CCGD). He also works closely with the Division of Gastrointestinal Oncology at DFCI and has helped establish an organoid and PDX repository derived from primary and metastatic pancreatic and colon cancer samples. Working with the CCGD, Dr. Hahn's laboratory has created a pipeline for the genomic characterization of consented patient derived samples. Dr. Weinstock is a medical oncologist and directs the DFCI Hematologic Malignancy PDX repository, which already contains >200 transplantable leukemia PDX models that have been cryopreserved and undergone genome-wide transcriptome analysis, targeted DNA sequencing, immunophenotyping, and additional molecular characterization. Thus, Core 1 has extensive experience in the processing, cryopreservation, flow cytometric analysis, purification, propagation, banking, and genomic characterization of primary specimens and tumor models, as well as their use in preclinical drug evaluation.

核心 1 – 项目摘要核心 1 的总体目标是提供银行所需的基础设施和专业知识原发性白血病、结肠癌和胰腺癌标本，建立患者来源的异种移植物（PDX），类器官和细胞模型，并将这些源自患者的资源提供给所有计划研究人员，从而促进 CSBC 研究人员在以下领域进行的转化和基于实验室的研究：项目 1 和 2。这两个项目都需要获取源自 PDX 和类器官的患者样本和细胞核心支持 3 种功能：(1) 冷冻保存和分配来自患有糖尿病的患者的原代细胞。白血病、结肠癌和胰腺癌，(2) 异种移植物的建立、表征和分布，这些疾病的类器官和细胞培养模型，以及（3）从原发性肿瘤中分离细胞群用于单细胞分析的样品和组织模型核心的功能包括记录和分析。跟踪知情同意、活组织、血浆或血清以及基因组的分离和冷冻保存患者样本中的 DNA 并将样本分发给 CSBC 研究人员。目前，我们现有的存储库中提供了白血病、结肠癌和胰腺肿瘤样本，可供以下人员使用：项目研究人员将从我们定期评估的患者中获取额外的样本。除了将原代细胞分配给胃肠道肿瘤和血液恶性肿瘤诊所外。项目调查员，Core 1 还将维护和分发一组经过精心挑选的 PDX，用于移植白血病细胞和原发性上皮肿瘤的方法。免疫缺陷小鼠的组织现已得到很好的建立，我们和其他人已经成功地使用 PDX 类器官培养方法将用于补充 PDX 工作，并将用于药物测试。提供了另一种传播和分离患者来源的上皮肿瘤细胞和基质细胞的方法 Core 1 将维护 PDX 模型和类器官库，并分发给项目研究人员作为核心 1 将由 William Hahn 博士和 David Weinstock 博士共同指导。 DFCI 癌症基因组发现中心 (CCGD) 的主任肿瘤学家，他还与 DFCI 癌症基因组发现中心 (CCGD) 密切合作。 DFCI 胃肠肿瘤科，帮助建立了类器官和 PDX 存储库与 CCGD 合作，从原发性和转移性胰腺癌和结肠癌样本中提取。哈恩的实验室创建了一个管道，用于对同意的患者衍生的基因组特征进行分析 Weinstock 博士是一名医学肿瘤学家，负责 DFCI 血液恶性肿瘤 PDX 存储库，其中已包含超过 200 个已冷冻保存的可移植白血病 PDX 模型遗传全基因组转录组分析、靶向 DNA 测序、免疫表型分析和因此，Core 1 在处理方面拥有丰富的经验，冷冻保存、流式细胞术分析、纯化、繁殖、存储和基因组表征主要标本和肿瘤模型，以及它们在临床前药物评价中的应用。