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

这个子项目是许多利用 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。 肿瘤细胞可以通过基因改变来增强其刺激免疫力的能力。 我们之前已经在I期临床试验中评估了慢性淋巴细胞白血病（B-CLL）疫苗，其中将两种免疫刺激基因（称为hCD 40 L和hIL-2）置于肿瘤细胞中并注射到患有这种疾病的患者中。 这种疫苗产生了特异性抗肿瘤反应，没有任何明显的副作用。 然而，这些好处是微不足道的，而且是短暂的。 为了尝试更多地了解为什么这种方法不能长期工作，我们研究了一种称为白血病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疫苗的接种时间将产生更长期的效果，减少肿瘤SP细胞，从而对肿瘤产生整体影响。 具体目标 确定用表达CD 40 L和分泌IL 2的B-CLL细胞延长免疫对肿瘤细胞侧群（SP）和非SP肿瘤细胞的影响。 确定延长免疫是否诱导和维持MHC限制性或非限制性抗肿瘤免疫应答。 评估延长疫苗接种时间表的安全性。

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. 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.