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 核心董事：Elizabeth Shpall 医学博士和 John McMannis 博士 抽象的 该 POI 的主要目标是改善慢性粒细胞白血病患者的治疗 （慢性粒细胞白血病）。提供特异性和最佳效力的抗肿瘤治疗可能会导致抗肿瘤效果的重大改善 功效和安全性。目标 1，良好生产规范 - 免疫评估 (GMP-IA) 核心 将优化生成针对恶性 CML 的 PRI 特异性 T 细胞的临床程序 细胞。然后，Core 将向项目 2 干细胞移植临床试验提供这些 PRI 特异性 T 细胞产品，试图根除移植后的微小残留病。随后，核心将在标准治疗环境中向项目 1 提供 PRI 特异性 CTL，试图消除伊马替尼治疗的 CML 患者的微小残留病。 GMP-IA 核心目标 2 将为项目 2 干细胞移植和单倍体相同 NK 细胞治疗方案提供人工自然杀伤 (NK) 细胞。此外，GMP-IA 核心将评估改进 NK 细胞生成程序的策略，该策略将用于该试验的后续队列。 GMP-IA 核心将负责如上所述的临床细胞产品的升级和验证研究，将帮助项目研究人员准备 IND 申请，协调向食品和药物管理局 (FDA) 提交的文件，并就相关事宜与 FDA 进行沟通细胞操作程序。 GMP-IA 核心的目标 3 对参加项目 1 和 2 免疫介导疗法临床试验的 CML 患者的外周血白细胞进行免疫评估。在拟议的研究中，我们将测量参加 PR 的患者的抗 CML 免疫力-1 疫苗和 PRI-CTL 试验，以根除项目 1 标准治疗后的微小残留病。项目 2 中 SCT 后接受新型 NK 或 PR1-CTL 细胞疗法的患者也将受到监测，以确定这些疗法产生的抗 CML 免疫力的持久性。由于项目 2 研究是在移植后免疫抑制的背景下进行的，并且这些疗法可能会对正常免疫稳态产生意想不到的影响，因此除了监测 NK 或 PRI-CTL 介导的抗 CML 之外，我们还将评估整体免疫状态 免疫v.