Core C: Cell Processing and Sample Collection

核心 C：细胞处理和样品采集

• 批准号: 10412944
• 负责人: Cameron John Turtle
• 金额: $ 12.07万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-28 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10412944
• 关键词: Acute Myelocytic Leukemia; Adoptive Immunotherapy; Adoptive Transfer; Affect; Allogenic; Area; Aspirate substance; Autologous; Biological Markers; Blood specimen; Bone Marrow; Cells; Clinic; Clinical; Clinical Trials; Collection; Correlative Study; Cryopreservation; Data; Decentralization; Development; Enrollment; Ensure; Floor; Formulation; Foundations; Fred Hutchinson Cancer Research Center; Freezing; Future; Gene-Modified; Goals; Grant; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Human; Human Engineering; Immunodeficient Mouse; Immunologics; Immunotherapy; In Vitro; Infusion procedures; Laboratory Research; Logistics; Methods; Modeling; Multiple Myeloma; Outcome; Patients; Procedures; Process; Production; Quality Control; Receptor Cell; Research; Running; Sampling; Structure of thyroid parafollicular cell; System; T cell therapy; T-Cell Depletion; T-Cell Receptor; T-Cell Receptor Genes; T-Lymphocyte; Testing; Tissue Sample; Transplant Recipients; Tumor-Derived; Validation; Vertebral column; WT1 gene; acute care; adult leukemia; antitumor effect; base; bench to bedside; cancer care; cancer therapy; chimeric antigen receptor; chimeric antigen receptor T cells; cost effective; data quality; engineered T cells; experimental study; improved; insight; manufacturing process; novel; phase 1 study; process optimization; quality assurance; research study; sample collection; tissue processing; trial comparing; tumor

PROJECT SUMMARY/ABSTRACT Cell Processing and Sample Collection: Core C This FHCRC Adult Leukemia Research Center (ALC) grant comprises proposals for three clinical trials: one trial of adoptive immunotherapy with WT1-specific T cell receptor (TCR) gene-modified T cells for acute myeloid leukemia (Project 1); one trial of adoptive immunotherapy using BCMA-specific chimeric antigen receptor (CAR)-modified T cells for multiple myeloma (Project 2); and one trial comparing methods of T cell depletion of donor grafts for allogeneic HCT (Project 3). Core C: Cell Processing and Sample Collection will support the activities of Projects 1-3. First, Core C will provide highly specialized facilities and expertise necessary to conduct current Good Manufacturing Practice (cGMP) production of TCR- and CAR-modified T cells for Projects 1-2 for treatment of patients enrolled in the clinical trials proposed in Projects 1-2. This effort will initially comprise validation cell processing runs (years 1-2) to qualify standard operating procedures for subsequent cGMP production, followed by cGMP production and release of genetically modified T cell products (years 1-5). Compared to decentralized cell processing managed by each separate project, consolidation of clinical cell processing within Core C will ensure that cGMP manufacturing is efficient and cost-effective, and performed with the optimal level of quality control (QC) and quality assurance (QA) oversight. Second, Core C will conduct studies to evaluate the effects of short-term storage in infusion medium or of cryopreservation on the potency of CAR- or TCR-modified T cells for clinical use. Although the potency of genetically modified T cells that are freshly formulated may be better than that of those that are stored, the ability to store and cryopreserve these products will be important for clinical logistics and for future delivery beyond phase 1 studies. We will conduct these studies using models in which human genetically modified T cells that have been stored under different conditions are administered to immunodeficient mice bearing human tumors, because we have found that data in these models of efficacy most accurately reflects outcomes in human engineered T cell clinical trials. Because the manufacturing processes may affect the capacity of genetically modified T cell products to tolerate storage, we will conduct these experiments using T cells that are manufactured using either a process involving multiple in vitro stimulations (Project 1) or a truncated process involving only a single stimulation (Project 2). The data will provide insight into whether important and frequently performed processing manipulations affect potency of genetically modified T cells. Third, Core C will provide a clinic-based facility to rapidly and efficiently process and distribute research samples from Projects 1-3 to FHCRC research laboratories and external collaborators. This will ensure data of the highest quality and uniformity is obtained from correlative research studies, maximizing the opportunity for bedside-to-bench research to guide new developments in adoptive immunotherapy and allogeneic HCT.

项目摘要/摘要 细胞处理和样本采集：CORE C FHCRC成人白血病研究中心(ALC)的这笔赠款包括三项临床试验的建议：一 WT1特异性T细胞受体基因修饰的T细胞过继免疫治疗急性白血病的实验研究 髓系白血病(项目1)；使用BCMA特异性嵌合抗原进行过继免疫治疗的一项试验 受体(CAR)修饰的T细胞治疗多发性骨髓瘤(项目2)；T细胞的一项试验比较方法 同种异体血细胞移植供者移植物的耗竭(项目3)。核心C：细胞处理和样本收集将 支持项目1-3的活动。首先，核心C将提供高度专业化的设施和专业知识 TCR和轿车改装T的现行良好制造规范(CGMP)生产的必要性 项目1-2的细胞，用于治疗项目1-2中提议的临床试验中登记的患者。这一努力 最初将包括验证单元处理运行(1-2年)，以鉴定以下标准操作程序 随后生产cGMP，随后生产cGMP并释放转基因T细胞 产品(1-5岁)。与由每个单独的项目管理的去中心化单元处理相比， 在Core C内整合临床细胞处理将确保cGMP的生产高效和 具有成本效益，并以最佳水平的质量控制(QC)和质量保证(QA)执行 疏忽。第二，Core C将进行研究，以评估在输液介质中短期储存的效果 或冷冻保存对临床使用的CAR或TCR修饰T细胞的效力的影响。尽管它的威力 新鲜配制的转基因T细胞可能比储存的要好， 储存和冷藏这些产品的能力对临床物流和未来的交付将是重要的 超越第一阶段研究。我们将使用模型进行这些研究，在模型中，人类转基因T细胞 将在不同条件下储存的细胞接种于免疫缺陷小鼠， 人类肿瘤，因为我们已经发现，这些模型中的数据最准确地反映了疗效 人类工程T细胞临床试验的结果。因为制造过程可能会影响 转基因T细胞产品耐受储存的能力，我们将使用T细胞进行这些实验 使用涉及多个体外刺激的过程(项目1)或使用 仅涉及单一刺激的截断过程(项目2)。这些数据将为我们提供关于 重要的和经常进行的处理操作会影响转基因T细胞的效力。 第三，Core C将提供以临床为基础的设施，以快速高效地处理和分发研究 从项目1-3到FHCRC研究实验室和外部合作者的样本。这将确保以下数据 最高质量和一致性来自相关研究，最大限度地增加了 床边到工作台研究，以指导过继免疫治疗和同种异体红细胞移植的新发展。