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

淋巴细胞趋化素和白细胞介素 2 基因 MODI 免疫的 I/II 期研究

• 批准号: 8166717
• 负责人: CHRYSTAL U LOUIS
• 金额: $ 0.99万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166717
• 关键词: Allogenic; Autologous; Cell Line; Cells; Computer Retrieval of Information on Scientific Projects Database; Consolidation Therapy; Diagnosis; Dose; Funding; Gene-Modified; Grant; IL2 gene; Immune response; Immunization; Immunization Schedule; Immunologics; Institution; Interleukin-2; Investigational Therapies; Measurable; Neuroblastoma; Newly Diagnosed; Patients; Phase; Polymerase Chain Reaction; Progression-Free Survivals; Protocols documentation; Randomized; Research; Research Personnel; Residual Neoplasm; Resources; Safety; Source; Stem cells; Toxic effect; Transplantation; Tumor Cell Line; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; chemokine; chemotherapy; clinical efficacy; cytokine; high risk; improved; safety testing; tumor

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. 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. 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 reaction pre- and post-vaccination. Secondary Objectives: 1. Estimate 3 year progression free survival (PFS) and overall survival (OS) in vaccinated patients.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们打算在接受单次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化疗患者中，测试2种同种异体神经母细胞瘤肿瘤细胞系疫苗组合的安全性、免疫学和临床疗效，其中一种疫苗经过基因修饰，可分泌IL-2和趋化因子组合。 本方案将作为I/IIa期研究进行，以评价将先前未研究的、未修饰的、经辐照的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-IL 2/Lptn中的安全性和毒性，该细胞系将作为疫苗给予诊断为高风险神经母细胞瘤的患者。 我们假设用未修饰的SKNLP与IL 2/Lptn基因修饰的SJNB-JF细胞系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应答，从而减少高危神经母细胞瘤患者的微小残留疾病并改善无进展和总生存率。在没有随机化的情况下，我们将无法明确说明MRD的任何损失是否可归因于移植或额外的免疫接种计划，但在免疫接种期间发生的MRD进行性降低，与针对肿瘤的免疫应答相关，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时失去抗肿瘤免疫应答，并且MRD随后恢复，那么这将进一步支持我们的假设。 主要目的： 1.评价基因修饰的、分泌IL-2/趋化因子的SJNB-JF-IL 2和SJNB-JF-Lptn细胞与未修饰的SKNLP神经母细胞瘤细胞系联合给药的重复免疫的安全性。 2.评估对这些免疫接种的免疫应答。 3.通过聚合酶链反应评价接种前后最小残留疾病负荷的变化。 次要目的： 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）。