A PHASE I/II STUDY USING ALLOGENEIC TUMOR CELL VACCINATION

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 神经母细胞瘤是一种导致显著发病率和死亡率的儿科癌症。作为第二常见的恶性实体瘤，它占所有儿童癌症死亡的10%以上。在目前的治疗中，4期高危疾病患者的总生存率仍低于30-40%，迫切需要改善这些儿童的治疗选择。我们和其他研究小组已经显示了使用神经母细胞瘤特异性免疫疗法的免疫学和临床疗效。由于神经母细胞瘤的异质性，当与过继性细胞和单克隆抗体治疗相比时，教导免疫系统靶向不同的肿瘤抗原库并使用更广泛的宿主效应机制与使用肿瘤细胞疫苗可以提供增加的抗肿瘤功效。在我们最后一次同种异体肿瘤细胞疫苗试验中，我们能够在复发/难治性疾病患者中诱导临床应答，包括完全缓解。然而，总体结果可能受到呈递的肿瘤抗原数量和肿瘤的抑制性微环境的限制。在本临床研究中，我们建议通过以下方式解决这些障碍：1）修改疫苗产品以增加呈递给免疫系统的肿瘤相关抗原的数量，以及2）将联合收割机疫苗接种与节拍口服环磷酰胺结合，后者已显示通过抗血管生成和抑制调节性T细胞来改变肿瘤微环境。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Neuroblastoma is a form of pediatric cancer that leads to significant morbidity and mortality. As the 2nd most common malignant solid tumor, it accounts for greater than 10% of all pediatric cancer deaths. With current therapy, overall survival remains less than 30-40% for patients with stage 4 high-risk disease and there is an urgent need for improved treatments options for these children. We and other groups have show immunological and clinical efficacy with the use of neuroblastoma-specific immunotherapy. Due to the heterogeneous nature of neuroblastoma, teaching the immune system to target a diverse tumor antigen repertoire and use a broader array of host effector mechanisms with the use of tumor cell vaccines may provide increased anti-tumor efficacy when compared to adoptive cellular and monoclonal antibody therapy. During our last allogeneic tumor cell vaccine trial, we were able to induce clinical responses, including complete remissions, in patients with relapsed/refractory disease. However, the overall results were likely limited by the number of tumor antigens presented and the inhibitory microenvironment of the tumor. In this clinical study, we propose to address these obstacles by 1) modifying the vaccine product to increase the number of tumor associated antigens presented to the immune system, and 2) combine vaccination with metronomic oral cytoxan which has been show to alter the tumor microenvironment via anti-angiogenesis and suppression of T regulatory cells.