Good Manufacturing Practice (GMP) and Immune Assessment Core

CML P01核心E：GMP免疫评估核心 核心董事：伊丽莎白·沙波尔医学博士和约翰·麦克曼尼斯博士 摘要 这一POI的主要目标是改善慢性粒细胞白血病患者的治疗 (CML)。提供特效和最佳有效的抗肿瘤治疗可能导致抗肿瘤的重大改善。 有效性和安全性。在目标1中，良好制造规范-免疫评估(GMP-IA)核心 将优化临床程序以产生针对恶性CML的PRI特异性T细胞 细胞。然后，Core将在干细胞移植环境中向Project 2临床试验提供这些PRI特异性T细胞产品，试图消除移植后最小的残留疾病。CORE随后将在标准治疗环境中向项目1提供PRI特异性CTL，试图消除接受伊马替尼治疗的CML患者的最小残留疾病。GMP-IA Core Aim 2将为Project 2干细胞移植和半相合NK细胞治疗方案提供经操纵的自然杀伤(NK)细胞。此外，GMP-IA核心将评估改进NK细胞生成程序的策略，该程序将在该试验的后续队列中使用。GMP-IA核心将负责上述临床细胞产品的升级和验证研究，将帮助项目调查人员准备IND申请，协调向食品和药物管理局(FDA)提交的文件，并就细胞操作程序与FDA进行沟通。 目的GMP-IA Core 3提供对参加项目1和2中免疫介导性治疗临床试验的CML患者外周血白细胞的免疫评估。在拟议的研究中，我们将测量参加PR-1疫苗和PRI-CTL试验的患者的抗CML免疫，以消除项目1中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细胞治疗的患者也将接受监测，以确定这些治疗所导致的抗CML免疫的持久性。由于项目2的研究是在移植后免疫抑制的情况下进行的，而且这些疗法可能会对正常的免疫稳态产生意想不到的影响，所以除了监测NK或PRI-CTL介导的抗CML外，我们还将评估整体免疫状态 免疫力。

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.