A PHASE I/II STUDY OF IMMUNIZATION WITH LYMPHOTACTIN AND INTERLEUKIN 2 GENE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们打算测试两种同种异体神经母细胞瘤细胞系疫苗组合的安全性、免疫学和临床疗效，其中一种疫苗已经过基因改造，可分泌IL-2和淋巴动蛋白的细胞因子/趋化因子组合，用于接受单一自体干细胞拯救作为巩固治疗的新诊断、高风险神经母细胞瘤患者的化疗。 该方案将作为一项I/IIa期研究进行，以评估将先前未研究的、未经修饰的辐射神经母细胞瘤细胞系(SKNLP)添加到研究的、安全剂量的基因修饰的、分泌IL-2/Lptn的神经母细胞瘤细胞系SJNB-JF-IL2/Lptn作为疫苗给被诊断为高危神经母细胞瘤的患者的安全性和毒性。 假设 我们推测，未修饰的SKNLP与IL2/Lptn基因修饰的SJNB-JF细胞株联合免疫将提供针对神经母细胞瘤的有效和可测量的免疫反应，从而减少微小的残留疾病，提高高危神经母细胞瘤患者的无进展和总体生存率。在没有随机化的情况下，我们将不能明确地说明MRD的任何损失是由于移植还是由于额外的免疫计划，但随着对肿瘤的免疫反应的发展，在免疫期间MRD的逐渐减少将有利于实验治疗的贡献。此外，如果患者在疫苗接种过程完成后失去了抗肿瘤免疫反应，而MRD随后又回来了，那么这将进一步支持我们的假设。 具体目标 主要目标： 1.评价基因修饰的分泌IL-2淋巴动素的SJNB-JF-IL2和SJNB-JF-Lptn细胞与未修饰的SKNLP神经母细胞瘤细胞联合重复免疫的安全性。 2.评估对这些免疫接种的免疫反应。 3.用聚合酶链式反应评估最小残留疾病负荷的变化 次要目标： 1.估计接种疫苗患者的3年无进展生存期(PFS)和总生存期(OS)。

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. We intend to test the safety, and immunologic and clinical efficacy of a combination of 2 allogeneic neuroblastoma tumor cell line vaccines, one of which has been genetically modified to secrete the cytokine/chemokine combination of IL-2 and lymphotactin, in patients undergoing chemotherapy for newly diagnosed, high risk neuroblastoma who receive single autologous stem cell rescue as consolidation therapy. This protocol will be carried out as a Phase I/IIa study to evaluate the safety and toxicity of adding a previously unstudied, unmodified, irradiated neuroblastoma cell line (SKNLP) to a studied, safe dose of a gene modified, IL-2/Lptn secreting neuroblastoma cell line SJNB-JF-IL2/Lptn to be given as a vaccine to patients diagnosed with high risk neuroblastoma. HYPOTHESIS We hypothesize that immunization with the unmodified SKNLP in conjunction with IL2/Lptn gene modified SJNB-JF cell lines will provide an effective and measurable immune response against neuroblastoma, resulting in diminished minimal residual disease and improved progression free and overall survival in patients with high-risk neuroblastoma. In the absence of randomization, we will not be able to state definitively whether any loss of MRD is attributable to the transplant or to the additional immunization schedule, but a progressive reduction in MRD occurring over the duration of the immunization period, associated with a developing immune response against the tumor, will favor a contribution from the experimental therapy. Moreover, if patients lose their anti-tumor immune response when the course of vaccination is complete, and MRD subsequently returns, then this will further support our hypothesis. SPECIFIC AIMS Primary Objectives: 1. Evaluate the safety of repeated immunization with gene-modified, IL-2 lymphotactin secreting SJNB-JF-IL2 and SJNB-JF-Lptn cells co-administered with the unmodified SKNLP neuroblastoma cell line. 2. Evaluate the immune response to these immunizations. 3. Evaluate changes in minimal residual disease load by polymerase chain par Secondary Objectives: 1. Estimate 3 year progression free survival (PFS) and overall survival (OS) in vaccinated patients.