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

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。 本研究假设，与用相同肽与KLH和QS-21作为佐剂制备的疫苗相比，用候选黑素瘤特异性肽的钥孔血蓝蛋白（KLH）脉冲的树突状Ag呈递细胞制备的疫苗是细胞毒性T淋巴细胞应答的上级“增强剂”。 目的是测量HLA-A*0201阳性IIB、IIC和/或III期黑色素瘤患者中这两组的毒性和免疫原性。 终点是1）当暴露于黑素瘤特异性肽和对照Ag时，外周血淋巴细胞中γ-干扰素的释放; 2）Ag特异性CD 8 + T细胞的比例; 3）基于树突细胞（DC）的细胞溶解测定中CD 8 + T细胞的抗肿瘤活性;和4）毒性特征。 这项随机、对照、非盲（脉冲DC组需要白细胞去除术）研究解决了一组患者中免疫治疗的优化问题，该组患者对这种一般方法表现出顺从和反应。

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.