Bone Marrow Grafting for Leukemia and Lymphoma

骨髓移植治疗白血病和淋巴瘤

• 批准号: 8848766
• 负责人: Robert S Negrin
• 金额: $ 270万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8848766
• 关键词: Acute Graft Versus Host Disease; Acute Myelocytic Leukemia; Allogenic; Animal Model; Antithymoglobulin; Autoimmune Diseases; Autologous; B-Lymphocytes; Biodiversity; Biological; Biological Models; Biology; Blood; Bone Marrow Transplantation; Breeding; CD8B1 gene; Cells; Cellular biology; Clinic; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Clinical Trials Network; Common Lymphoid Progenitor; Complex; Effector Cell; Evaluation; Follicular Lymphoma; Functional disorder; Goals; Graft-Versus-Tumor Induction; Hematologic Neoplasms; Hematopoietic; Human; Image; Immune; Immune response; Immunoglobulin Genes; Immunoglobulins; Immunosuppressive Agents; Infection; Instruction; Intervention; Kidney Transplantation; Killer Cells; Lymphatic Irradiation; Malignant Neoplasms; Marrow; Memory; Molecular; Morbidity - disease rate; Multiple Myeloma; Nature; Organ Transplantation; Outcome; Patient Care; Patients; Pharmaceutical Preparations; Phase; Population; Prevention; Program Research Project Grants; Publishing; Reaction; Recovery; Recurrent disease; Refractory; Regulatory T-Lymphocyte; Research Personnel; Research Project Grants; Sampling; Solid; Solid Neoplasm; Stem cells; Structure; T-Cell Receptor; T-Lymphocyte; Technology; Therapeutic; Translating; Translations; Transplantation; Transplantation Tolerance; Universities; Weaning; Work; base; cancer cell; cancer therapy; chronic graft versus host disease; clinical efficacy; cytokine; deep sequencing; disorder prevention; effective therapy; genetic analysis; graft vs host disease; hematopoietic cell transplantation; immune function; improved; innovation; insight; leukemia/lymphoma; member; molecular imaging; mortality; novel; novel strategies; prevent; progenitor; programs; reconstitution; translational study; vaccination strategy

DESCRIPTION (provided by applicant): This Program Project Grant (PPG) seeks continued support for basic and translational clinical studies in the setting of hematopoietic cell transplantation (HCT). These studies serve as a paradigm for cellular therapeutics and the exploration of immune function for the treatment of cancer. The PPG is composed of five interactive Projects and four Cores focused on the themes of graft vs host disease biology and prevention, disease relapse treatment and prevention and immune reconstitution. The Program utilizes innovative animal modeling, imaging, molecular biological assessment of immunoglobulin and T cell receptor sequencing and novel clinical trial interventional studies with highly purified cell populations to explore the fundamental aspects of transplantation biology and improve outcomes for patients undergoing both autologous and allogeneic HCT. The Projects focus on different aspects of immune effector (conventional and memory CD4+ and CD8+ T cells, cytokine induced killer cells) and regulatory (Treg, NK-T) cell biology, vaccination strategies (CpG stimulated cancer cells), common lymphoid progenitor cell biology and immune recovery in a highly interactive and complementary fashion. In each of the Projects both fundamental biological explorations in animal models and clinical translation in phase 1/11 trials are proposed aimed at enhancing the clinical efficacy of HCT. The Projects and Project leaders are highly interactive using similar animal models, imaging strategies, novel approaches to analysis of T cell receptor sequencing to analyze distinct yet iterative approaches to answer fundamental biological questions and explore translation to the clinic. The four Cores provide administrative, clinical trial, molecular, sample distribution and cellular manufacture support. Ou hypothesis is that through the study of the cellular components of hematopoietic and immunological progenitor, regulatory and effector cells will result in novel insights into improvin immune function resulting in more effective therapy for patients with serious hematological malignancies.

描述（由申请人提供）：该计划项目赠款（PPG）在造血细胞移植（HCT）的情况下寻求基础和转化临床研究的持续支持。这些研究是细胞疗法的范式，并探索了治疗癌症的免疫功能。 PPG由五个互动项目和四个核心组成，这些核心重点介绍了移植物与宿主疾病生物学和预防，疾病复发治疗以及预防以及免疫重建的主题。该计划利用了对免疫球蛋白和T细胞受体测序的创新动物建模，成像，分子生物学评估以及具有高度纯化细胞群体的新型临床试验介入研究，以探索移植生物学的基本方面，并改善接受自动生物和同种HCT患者的成果。这些项目侧重于免疫效应子（常规和记忆CD4+和CD8+ T细胞，细胞因子诱导的杀伤细胞）和调节性（Treg，NK-T）细胞生物学，疫苗接种策略（CPG刺激癌细胞），常见淋巴样祖细胞生物学和高度交互性恢复和互补的免疫恢复。在每个项目中，都提出了旨在增强HCT临床功效的1/11试验中动物模型中的基本生物学探索和临床翻译。使用类似的动物模型，成像策略，分析T细胞受体测序的新方法，分析不同但迭代的方法来回答基本的生物学问题并探索转化为诊所。这四个核心提供行政，临床试验，分子，样品分布和细胞制造支持。 OU假设是，通过研究造血和免疫学祖细胞的细胞成分，调节性和效应细胞将导致对改善免疫功能的新见解，从而为严重的血液恶性肿瘤患者提供更有效的治疗。