MARKERS TO IMPROVE ASSESSMENT OF TREATMENT EFFICACY FOR METASTATIC MELANOMA

该项目的研究重点是多式联运治疗。 手术治疗的AJCC III期黑色素瘤患者中，活性特异性 免疫疗法(PMCV；多价黑色素瘤细胞疫苗)和IFNpha-2b在 一项多中心随机第三期临床试验。这件事的成功 临床试验需要终点来确定治疗效果。这个 无病存活期和总存活率是确定的 测量的临床终点，但他们的评估需要长时间的跟踪- 向上。此外，它们也不能用作监测早期 对治疗的反应或预测复发转移疾病。 项目二将重点研究预后分子标志物(PMM)。 评估它们在识别疾病状态和诊断疾病方面的临床效用 在出现任何临床明显变化之前，对治疗的反应。 预后分子标志物将被定性地评估为半 通过使用大规模多标记反转来定量 逆转录聚合酶链式反应(RT-PCR)和自动化Southern 我们建立了印迹分析体系。RT-PCR和Southern印迹分析 将用于：(1)验证PMM用于检测亚临床复发 疾病和肿瘤进展的决定因素；(2)评估PMM临床 预测治疗干预措施临床疗效的实用价值 在接受手术的黑色素瘤患者中，PMCV和IFNpha-2b；以及，(3) PMM与相应的特异性细胞介导的反应相关 (迟发型超敏反应皮肤试验)和抗体反应 免疫原性黑色素瘤相关抗原。后一项研究将是 重点介绍了已知的免疫原性MAA及其重组的PMM 蛋白质将提供一个极好的患者资源来评估临床 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.