ADMINISTRATION OF PERIPHERAL BLOOD T-CELLS AND EBV SPECIFIC CTLS

外周血 T 细胞和 EBV 特异性 CTLS 的施用

• 批准号: 7374994
• 负责人: HEIDI V RUSSELL
• 金额: $ 0.62万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374994
• 关键词: ADMINISTRATION; PERIPHERAL; BLOOD; CELLS; EBV

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. Neuroblastoma, the most common extracranial solid tumor of childhood, affects approximately 600 children a year in the United States. When the tumor occurs in infants (children under 1 year of age), it is frequently localized and responds well to therapy. Even disseminated disease can be eradicated in about 75% of infants and, indeed, may undergo spontaneous remission. In older children (over 1 year of age), the prognosis is far worse. Although patients with localized disease may still be cured by conventional therapy, 70% or more of those with disseminated tumor can be expected to relapse within 3 years, and virtually none of this subgroup will become long-term survivors. Over the past decade, attempts to improve the outcome of advanced neuroblastoma have focused on greater intensification of the induction and consolidation phases of chemo-radiotherapy, with or without stem cell rescue. Despite improvements in remission rates, long term survival remains poor. This failure has lead to a resurgence of interest in alternative methods of disease eradication, immune modulation as one particular option. The primary objectives of this study are: 1) 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 in patients with neuroblastoma who have been lymphodepleted by CD45 monoclonal antibodies (MAbs). Secondary objectives are: 1) 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; and 2) To determine anti-tumor effects of transduced peripheral blood T-cells and EBV specific CTLs in vivo.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。神经母细胞瘤是儿童期最常见的颅外实体瘤，在美国每年约有600名儿童受到影响。当肿瘤发生在婴儿（1岁以下的儿童）时，它通常是局部的，对治疗反应良好。即使是播散性疾病也可以在大约75%的婴儿中根除，而且确实可以自发缓解。在年龄较大的儿童（1岁以上）中，预后更差。虽然局部病变的患者仍可以通过常规治疗治愈，但70%或更多的播散性肿瘤患者预计会在3年内复发，几乎没有一个亚组会成为长期生存者。在过去的十年中，试图改善晚期神经母细胞瘤的结果集中在更大的强化诱导和巩固阶段的化学-放射治疗，有或没有干细胞救援。尽管缓解率有所提高，但长期生存率仍然很差。这一失败导致了对疾病根除的替代方法的兴趣的复苏，免疫调节作为一种特定的选择。 本研究的主要目的是：1）评估递增剂量的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细胞在已被CD 45单克隆抗体（MAb）淋巴细胞清除的神经母细胞瘤患者中的安全性。次要目的是：1）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;和2）确定转导的外周血T细胞和EBV特异性CTL在体内的抗肿瘤作用。