MARKERS TO IMPROVE ASSESSMENT OF TREATMENT EFFICACY FOR METASTATIC MELANOMA

该项目的研究重点是多模式治疗 AJCC III期黑色素瘤患者的手术，活性特异性 免疫疗法（PMCV;多价黑色素瘤细胞疫苗）和IFN α-2b， 多中心随机III期临床试验。 的成功 临床试验需要确定疗效的终点。 的 无病生存期和总生存期已明确确定 测量临床终点，但其评估需要长时间的随访- 起来 此外，它们不能用作监测早期 治疗反应或预测复发性转移性疾病。 项目II将重点研究预后分子标志物（PMM） 评估其在识别疾病状态中的临床效用， 在有任何临床上明显的变化之前，对治疗的反应。 预后分子标志物将进行定性评估， 通过采用大规模多标记反向 转录酶-聚合酶链反应（RT-PCR）和自动Southern杂交 我们建立了一个印迹分析系统。 RT-PCR和Southern印迹分析 将用于：（1）验证PMM用于检测亚临床复发性 疾病和肿瘤进展的决定因素;（2）评估PMM临床 在预测治疗干预的临床疗效中的效用 在接受手术的黑色素瘤患者中，PMCV和IFN α-2b;以及，（3） 将PMM与相应的特异性细胞介导的反应相关联 （迟发型超敏反应皮肤试验）和抗体反应 免疫原性黑素瘤相关抗原（MAA）。 后一项研究将是 重点关注PMM，其是已知的免疫原性MAA， 蛋白质将提供一个很好的病人资源，以评估临床 PMM的效用

The Program Project's investigational focus is on the multimodal treatment of AJCC Stage III melanoma patients by surgery, active specific immunotherapy (PMCV; polyvalent melanoma cell vaccine), and IFNalpha-2b in a multicenter randomized Phase III clinical trial. The success of this clinical trial requires endpoints for determining treatment efficacy. The duration of disease-free and overall survival are well established measured clinical endpoints but their assessment requires lengthy follow- up. Also, they cannot be used as criteria for monitoring the early response to therapy or predicting recurrent metastatic disease. Project II will focus on investigating prognostic molecular markers (PMM) to assess their clinical utility in identifying disease status and response to therapy before there is any clinically evident change. Prognostic molecular markers will be assessed qualitatively an semi- quantitatively by employing a large-scale multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) and automated Southern blot assay system we have established. RT-PCR and Southern blot assays will be used to: (1) validate PMM for detection of subclinical recurrent disease and as determinants of tumor progression; (2) assess PMM clinical utility in predicting the clinical efficacy of therapeutic interventions in melanoma patients receiving surgery, PMCV and IFNalpha-2b; and, (3) correlate PMM with corresponding specific cell-mediated responses (delayed-type hypersensitivity skin tests) and antibody responses to immunogenic melanoma-associated antigens (MAA). The latter study will be focused on PMM which are known immunogenic MAA and for which recombinant proteins will provide an excellent patient resource to assess the clinical utility of PMM.