CLINICAL TRIAL: PROLONGED IMMUNIZATION WITH AUTOLOGOUS CD-40 LIGAND AND IL-1-EX

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。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 可以对肿瘤细胞进行基因改造，以提高它们刺激免疫的能力。我们此前在I期临床试验中评估了一种慢性淋巴细胞白血病(B-CLL)疫苗，将两种免疫刺激基因(称为hCD40L和hIL-2)植入肿瘤细胞，并注射到患有这种疾病的患者体内。这种疫苗产生了特异性的抗肿瘤反应，没有任何明显的副作用。然而，好处很小，而且持续时间很短。为了试图更多地了解为什么这种方法不能长期有效，我们观察了一种名为白血病SP细胞的肿瘤细胞，然后通过延长疫苗接种时间对整个肿瘤产生后续影响。 假设 延长B-CLL疫苗接种时间会产生较长期的效应，减少肿瘤SP细胞，从而影响肿瘤的整体。 具体目标 目的：探讨CD40L表达和IL-2分泌的B-CLL细胞长期免疫对肿瘤细胞副群体(SP)和非SP群体肿瘤细胞的影响。 确定延长免疫后是否诱导和维持MHC限制性或非限制性抗肿瘤免疫反应。 评估延长的疫苗接种计划的安全性。

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. Tumor cells can be genetically changed to increase their ability to stimulate immunity. We have previously evaluated a Chronic Lymphocytic Leukemia (B-CLL), vaccine in a Phase I clinical trial where two immunity stimulating genes (called hCD40L and hIL-2) are placed into tumor cells and injected into patients with this disease. This vaccine produced a specific anti-tumor response without any significant side effects. However, the benefits were minor and short lived. To try and learn more about why this approach was not working long-term we looked at a type of tumor cell called the leukemic SP cells, and then a subsequent effect on the tumor as a whole, by prolonging the period of vaccination. HYPOTHESIS Prolonging the period of B-CLL vaccination will produce a longer term effect, decreasing tumor SP cells, thereby effecting the tumor a whole. SPECIFIC AIMS To determine the effects of prolonged immunization with CD40L expressing and IL2 secreting B-CLL cells on the Side Population (SP) of tumor cells, and on non-SP tumor cells. To determine whether MHC-restricted or unrestricted anti-tumor immune responses are induced and sustained by the prolonged immunization. To assess the safety of the prolonged vaccination schedule.