ADMINISTRATION OF PERIPHERAL BLOOD T-CELLS AND EBV SPECIFIC CTLS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。神经母细胞瘤是儿童时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，实际上，可能会自发缓解。在年龄较大的儿童（1岁以上），预后要差得多。虽然局部疾病患者仍可通过常规治疗治愈，但70%或更多的播散性肿瘤患者可在3年内复发，而且几乎没有一个亚组患者能成为长期幸存者。在过去的十年中，改善晚期神经母细胞瘤预后的尝试集中在更大程度上强化化疗的诱导和巩固阶段，有或没有干细胞救援。尽管缓解率有所改善，但长期生存率仍然很低。这一失败导致人们重新关注根除疾病的替代方法，免疫调节是其中一个特别的选择。本研究的主要目的是：1)评价递增剂量14g2a的安全性。zeta嵌合受体转导了自体EBV特异性细胞毒性t淋巴细胞（EBV- ctl）和14g2a。在CD45单克隆抗体（mab）导致淋巴细胞减少的神经母细胞瘤患者中，zeta转导了自体外周血t细胞。次要目标是：1)确定这两种输注细胞类型在体内的生存和功能差异，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；2)在体内检测转导的外周血t细胞和EBV特异性ctl的抗肿瘤作用。

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.