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 细胞处理和样品收集：核心C 这个FHCRC成人白血病研究中心（ALC）赠款包括三个临床试验的建议：一个 WT1特异性T细胞受体（TCR）基因改性T细胞的收养免疫疗法试验急性 髓样白血病（项目1）；使用BCMA特异性嵌合抗原的收养免疫疗法试验 多发性骨髓瘤的受体（CAR）修饰的T细胞（项目2）；和一项比较T细胞方法的试验 同种异体HCT的供体移植物的耗竭（项目3）。 Core C：细胞处理和样品收集将 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 进行当前的良好制造实践（CGMP）生产TCR和CAR修饰T 项目1-2的细胞治疗项目1-2中提出的临床试验的患者的治疗细胞。这项努力 最初将包括验证单元格处理（1-2年），以符合标准操作程序 随后的CGMP产生，然后产生CGMP并释放转基因T细胞 产品（1 - 5年）。与每个单独项目管理的分散小区处理相比， 核心C内的临床细胞处理的合并将确保CGMP制造有效，并且 具有成本效益，并以最佳的质量控制水平（QC）和质量保证（QA）执行 监督。其次，Core C将进行研究以评估短期存储在输注介质中的影响 或用于临床使用的CAR或TCR修饰T细胞效力的冷冻保存。虽然效力 新鲜配制的转基因T细胞可能比存储的T细胞更好 能够存储和冷冻水果这些产品对于临床物流和将来的交付至关重要 超越第1阶段研究。我们将使用人类遗传修改T的模型进行这些研究 在不同条件下存储的细胞被给予免疫缺陷的小鼠轴承 人类肿瘤，因为我们发现这些功效模型中的数据最准确地反映了 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细胞产物可耐受存储的能力，我们将使用t进行这些实验 使用涉及多个体外刺激（项目1）或A的过程制造的单元 仅涉及单个刺激的截断过程（项目2）。数据将提供有关是否是否 重要且经常执行的处理操作会影响转基因T细胞的效力。 第三，核心C将提供基于诊所的设施，以快速有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。这将确保数据的数据 最高质量和均匀性是从相关研究获得的，最大化的机会 床头到基础的研究指导收养免疫疗法和同种异体HCT方面的新发展。