Good Manufacturing Practice (GMP) and Immune Assessment Core

良好生产规范 (GMP) 和免疫评估核心

• 批准号: 8000169
• 负责人: Elizabeth J Shpall
• 金额: $ 39.88万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8000169
• 关键词: Allogenic; Cell Therapy; Cell Transplantation; Cells; Chronic Myeloid Leukemia; Clinical; Clinical Trials; Clinical assessments; Cytotoxic T-Lymphocytes; Doctor of Philosophy; Dose; Enrollment; Generations; Grant; Health; Hematopoietic; Homeostasis; Imatinib; Immune; Immune system; Immunity; Immunosuppression; Instruction; Lead; Leukocytes; Malignant - descriptor; Measures; Mediating; Methods; Monitor; Natural Killer Cells; Patients; Phenotype; Preparation; Procedures; Progressive Disease; Protocols documentation; Research Personnel; Residual Neoplasm; Safety; Sampling; Stem cell transplant; T-Lymphocyte; Therapeutic; Transplantation; United States Food and Drug Administration; Vaccines; abstracting; cohort; graft vs host disease; high risk; improved; leukemia; novel; outcome forecast; peripheral blood; pre-clinical; tumor; validation studies

CML P01 Core E: GMP- Immune Assessment Core Core Directors: Elizabeth Shpall MD and John McMannis PhD Abstract The primary objective of this POI is to improve the treatment of patients with chronic myelogenous leukemia (CML). Providing speciflc and optimally potent anti-tumor therapy could result in major improvements in antitumor efficacy and safety. In Aim 1, the Good Manufacturing Practice-Immune Assessment (GMP-IA) Core will optimize the clinical procedures for the generation of PRI-specific T cells that target malignant CML cells. The Core will then provide those PRI-specific T cell products to the Project 2 clinical trial in the stem cell transplant setting, in attempt to eradicate minimal residual disease post-transplant. The Core will subsequentiy provide the PRI-specific CTLs to Project 1 in the standard-therapy setting, in attempt to eliminate minimal residual disease in imatinib treated CML patients. The GMP-IA Core Aim 2 will provide manipulated natural killer (NK) cells for the Project 2 stem cell transplantation plus haplo-identical NK cell therapy protocol. Additionally, the GMP-IA Core will evaluate strategies to Improve the NK cell generation procedure, which will be used in later cohorts of that trial. The GMP-IA Core will be responsible for the upscale and validation studies for the clinical cellular products as described above, will aid project investigators preparation of the IND applications, orchestrate the submissions to the Food and Drug Administration (FDA) and communicate with FDA regarding the cellular manipulation procedures. Aim 3 of the GMP-IA Core provides immune assessment of peripheral blood leukocytes from CML patients enrolled in clinical trials of immune mediated therapies in Projects 1 and 2. In the proposed studies, we will measure anti-CML Immunity in patients enrolled in the PR-1 vaccine and PRI-CTL trials to eradicate minimal residual disease following standard-therapy in Project 1. Patients receiving novel NK or PR1-CTL cellular therapies post-SCT in Project 2 will also be monitored to determine the persistence of anti-CML immunity resulting from these therapies. Because the Project 2 studies occur in the context of immunosuppression post-transplant, and because these therapies may lead unexpected effects on normal immune homeostasis, we will assess overall Immune status in addition to monitoring NK- or PRI-CTL-mediated anti-CML immunitv.

CML P01核心E：GMP-免疫评估核心 核心主管：伊丽莎白·谢帕尔（Elizabeth Shpall）和约翰·麦克马尼斯（John McMannis）博士 抽象的 该POI的主要目的是改善慢性髓性白血病患者的治疗 （CML）。提供指定和最佳有效的抗肿瘤疗法可能会导致抗肿瘤的重大改善 功效和安全性。在AIM 1中，良好的制造实践免疫评估（GMP-IA）核心 将优化靶向恶性CML的PRI特异性T细胞的临床程序 细胞。然后，核心将在干细胞移植设置的Project 2临床试验中提供这些PRI特异性T细胞产品，以试图消除移植后最小残留疾病。核心将随后在标准治疗环境中为项目1提供PRI特异性CTL，以消除伊马替尼治疗的CML患者中最小的残留疾病。 GMP-IA核心AIM 2将为项目2干细胞移植加单利用的NK细胞治疗方案提供操纵的天然杀手（NK）细胞。此外，GMP-IA核心将评估改善NK细胞生成程序的策略，该过程将用于该试验的后期同类。 GMP-IA核心将负责如上所述的临床细胞产品的高档和验证研究，将有助于项目研究人员准备IND应用程序，协调对食品和药物管理局（FDA）的提交，并与FDA与FDA进行有关细胞操作程序的沟通。 GMP-IA核心的目标3提供了来自项目1和2的免疫介导疗法的临床试验的CML患者的外周血白细胞的免疫评估。在拟议的研究中，我们将测量在PRI-1疫苗和PRI-CTL试验中均可估算抗CML免疫的抗CML免疫，以擦除pri-ctl试验的新型疾病。项目2中SCT后的PR1-CTL细胞疗法也将受到监测，以确定这些疗法引起的抗CML免疫的持续性。由于项目2研究发生在移植后免疫抑制的背景下，并且由于这些疗法可能对正常的免疫稳态产生意外影响，因此除了监测NK或PRI-CTL介导的抗CML外，我们还将评估总体免疫状态 免疫。