DENDRITIC CELLS VERSUS MONTANIDE TO STIMULATE ANTI-TUMOR IMMUNITY IN MELANOMA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究假设，与以KLH和QS-21为佐剂的相同多肽制备的疫苗相比，用候选黑色素瘤特异性多肽的锁孔帽状血蓝蛋白(KLH)冲击的树突状抗原提呈细胞制备的疫苗是更好的细胞毒性T淋巴细胞反应的“助推器”。目的是评估这两种药物对人类白细胞抗原A*0201阳性的IIB期、IIC期和/或III期黑色素瘤患者的毒性和免疫原性。终点是：1)当暴露于黑色素瘤特异性多肽和对照Ag‘s时，外周血淋巴细胞释放γ-干扰素；2)Ag特异性CD8+T细胞的比例；3)基于树突状细胞(DC)的细胞溶解试验中CD8+T细胞的抗肿瘤活性；以及4)毒性特征。这项随机、对照、非盲法(脉冲DC组需要白细胞分离)的研究致力于优化一组患者的免疫治疗，这些患者被证明对这种一般方法是顺从和有效的。

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. This study hypothesizes that vaccines prepared with dendritic Ag-presenting cells pulsed with candidate melanoma-specific peptides' keyhole limpet hemocyanin (KLH) are superior "boosters" of the cytotoxic T-lymphocyte response as compared to vaccines prepared with the same peptides with KLH and QS-21 as adjuvants. The objective is to measure toxicity and immunogenicity in these two arms in patients with HLA-A*0201 positive stage IIB, IIC and/or III melanoma. The endpoints are 1) release of gamma-interferon in peripheral blood lymphocytes when exposed to the melanoma-specific peptides and control Ag's; 2) proportion of Ag-specific CD8+ T cells; 3) anti-tumor activity of CD8+ T cells in a dendritic cell (DC)-based cytolysis assay; and 4) toxicity profile. This randomized, controlled, unblinded (pulsed DC group requires leukopheresis) study addresses optimization of immunotherapy in a group of patients shown to be amenable and responsive to this general approach.