CLINICAL INVESTIGATION OF ACTIVE SPECIFIC IMMUNOTHERAPY OF MALIGNANT MELANOMA

这笔赠款的长期目标是发展 有效的恶性黑色素瘤治疗性疫苗。项目III的 是对一种辐照多价黑色素瘤细胞活疫苗的评价 (PMCV)。该项目有四个具体目标： 1.我们将进行PMCV的多中心随机第三阶段试验 AJCC III期黑色素瘤的术后辅助免疫治疗。这个 控制臂将是干扰素α2b(IFNpha-2b)，它最近已经 已经得到了FDA的批准。因为PMCV的毒性要低得多 比IFNpha-2b，疫苗将是首选的佐剂，如果它的 临床疗效证明与干扰素α-2b相当。 2.确定新的免疫学和分子标志物是否可以 用于检测亚临床转移性黑色素瘤并量化反应 到辅助治疗。我们假设这些新技术可以用来 作为预测辅助治疗结果的分层因素 对于没有临床证据的黑色素瘤患者 做手术。 3.确定对临床影响最大的免疫反应 参加第三阶段试验的PMCV接受者的结果。我们的目标是 开发一种可作为原型的免疫反应模型 监测黑色素瘤患者的疫苗治疗。 4.开展一系列试点研究(第一/第二阶段)，以确定是否 针对肿瘤相关抗原的免疫反应可以通过以下方式增强 PMCV免疫治疗联合细胞因子治疗黑色素瘤 (例如，IFNpha-2b)或作为有效佐剂的诱导剂 动物模型中的肿瘤排斥反应。

The long-term objective of this grant has been the development of effective therapeutic vaccines against malignant melanoma. Project III's is the evaluation of a living irradiated polyvalent melanoma cell vaccine (PMCV). This project has four Specific Aims: 1. We will conduct a multicenter randomized Phase III trial of PMCV as a postsurgical adjuvant immunotherapy in AJCC Stage III melanoma. The control arm will be interferon alpha 2b (IFNalpha-2b), which has recently been approved by the FDA. Because PMCV has a much lower toxicity profile than IFNalpha-2b, the vaccine would be the preferred adjuvant if its clinical efficacy proves comparable to that of IFNalpha-2b. 2. To determine whether new immunological and molecular markers can be used to detect subclinical metastatic melanoma an quantitate the response to adjuvant therapy. We hypothesize that these new techniques can be used as stratification factors in predicting the outcome of adjuvant therapy for melanoma patients who have no clinical evidence of disease following surgery. 3. Determine the immune response that optimally impacts the clinical outcome of PMCV recipients enrolled in the Phase III trial. Our goal is to develop an immune response model that can serve as a prototype for monitoring vaccine therapy in patients with melanoma. 4. Conduct a series of pilot studies (Phase I/II) to determine whether the immune response against tumor-associated antigens can be enhanced by combining PMCV immunotherapy with cytokines that have activity in melanoma (e.g., IFNalpha-2b) or agents that are effective adjuvants for inducing tumor rejection responses in animal models.