CLINICAL TRIAL: ADMINISTRATION OF PERIPHERAL BLOOD T-CELLS AND EBV SPECIFIC CTLS

临床试验：外周血 T 细胞和 EBV 特异性 CTLS 的施用

• 批准号: 7950600
• 负责人: CHRYSTAL U LOUIS
• 金额: $ 0.27万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950600
• 关键词: Animals; Antigens; Autologous; Behavior; Cell Survival; Cells; Child; Clinical; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Disease; Dose; EBV-Specific Cytotoxic T-Lymphocyte; Embryo; Funding; Gene-Modified; Grant; Immune system; Immunotherapy; In Vitro; Institution; Kinetics; Malignant - descriptor; Measures; Monoclonal Antibodies; Neuroblastoma; Neuroectoderm; PTPRC gene; Patients; Research; Research Personnel; Research Support; Resources; Safety; Signal Transduction; Sorting - Cell Movement; Source; Specificity; T-Lymphocyte; Therapeutic Monoclonal Antibodies; Transgenes; United States National Institutes of Health; Vaccines; cell type; cytokine; cytotoxic; in vivo; man; overexpression; peripheral blood; receptor; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Primary Objective To evaluate the safety of escalating doses of 14g2a.zeta chimeric receptor transduced autologous EBV specific cytotoxic T-lymphocytes (EBV-CTL)and 14g2a.zeta transduced autologous peripheral blood T-cells administered to patients with Neuroblastoma who have been lymphodepleted by CD45 monoclonal antibodies (MAbs). Secondary Objectives To determine the differential survival and function of these two infused cell-types in vivo, in particular to determine if chimeric receptor transduced EBV-CTLs survive longer than transduced peripheral-blood T-cells. To determine anti-tumor effects of transduced peripheral blood T-cells and EBV specific CTLs in vivo. The concept of exploiting the immune system to eradicate disease has had a long currency in neuroblastoma research, supported by many aspects of the tumor's biologic behavior, including spontaneous regression in younger children. In addition, because neuroblastoma is derived from embryonic neuroectoderm, it expresses antigens not widely detected in non-embryonic tissues11, and may overexpress other cellular antigens. Finally, in animals and in man, neuroblastoma cells are susceptible to cytotoxic effector mechanisms both in vitro and in vivo.13-15 Clinical immunotherapy for neuroblastoma has taken many forms which may be loosely classified into vaccine / cytokine approaches or the use of therapeutic monoclonal antibodies. By measuring the level of the transgene in peripheral blood we will be able to estimate the overall kinetics of gene- modified T-cell survival and determine whether expansion or persistence occures in vivo. Even if CTL derived signal does persist it is possible that the transgene-positive cells we detect will have lost one or other of their specificities for EBV and neuroblastoma. We will be able to use FACS sorting of tetramer positive cells to discover whether or not they retain their bifunctional activity against malignant and EBV-infected target cells.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 主要目的 评价向已被CD 45单克隆抗体（MAb）淋巴细胞耗竭的神经母细胞瘤患者施用递增剂量的14g2a.zeta嵌合受体转导的自体EBV特异性细胞毒性T淋巴细胞（EBV-CTL）和14g2a.zeta转导的自体外周血T细胞的安全性。 次要目的 确定这两种输注细胞类型在体内的差异存活和功能，特别是确定嵌合受体转导的EBV-CTL是否比转导的外周血T细胞存活更长。 确定转导的外周血T细胞和EBV特异性CTL的体内抗肿瘤作用。 利用免疫系统来根除疾病的概念已经有了一个 长期货币在神经母细胞瘤研究，支持的许多方面， 肿瘤的生物学行为，包括年幼儿童的自发消退。此外，由于神经母细胞瘤来源于胚胎神经外胚层，它表达的抗原在非胚胎组织中未被广泛检测到11，并且可能过度表达其他细胞抗原。最后，在动物和人类中，神经母细胞瘤细胞在体外和体内均易受细胞毒性效应机制的影响。13 -15神经母细胞瘤的临床免疫疗法有多种形式，可大致分为疫苗/细胞因子方法或使用治疗性单克隆抗体。 通过测量外周血中转基因的水平，我们将能够估计基因修饰的T细胞存活的总体动力学，并确定体内是否发生扩增或持续。即使CTL衍生的信号持续存在，我们检测到的转基因阳性细胞也可能已经失去了它们对EBV和神经母细胞瘤的一种或另一种特异性。我们将能够使用四聚体阳性细胞的FACS分选来发现它们是否保留其针对恶性和EBV感染的靶细胞的双功能活性。