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.
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