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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究假设，与以KLH和q -21作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肽的锁孔帽贝血青素（KLH）脉冲的树突状ag呈递细胞制备的疫苗是细胞毒性t淋巴细胞反应的优越“助推器”。目的是测量这两组HLA-A*0201阳性的IIB、IIC和/或III期黑色素瘤患者的毒性和免疫原性。终点是1)暴露于黑色素瘤特异性肽和对照Ag时外周血淋巴细胞释放γ -干扰素；2) ag特异性CD8+ T细胞比例；3)基于树突状细胞（DC）的细胞溶解实验中CD8+ T细胞的抗肿瘤活性；4)毒性分析。这项随机、对照、非盲（脉冲DC组需要白细胞去除）的研究解决了一组患者免疫治疗的优化问题，这些患者显示出对这种一般方法的适应性和反应性。

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. 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.