CLINICAL INVESTIGATION OF ACTIVE SPECIFIC IMMUNOTHERAPY OF MALIGNANT MELANOMA

这项赠款的长期目标是发展 针对恶性黑素瘤的有效治疗性疫苗。 项目三 是对一种活的辐射多价黑色素瘤细胞疫苗的评估， （PMCV）。 该项目有四个具体目标： 1. 我们将进行一项多中心、随机、III期PMCV试验， AJCC III期黑素瘤的术后辅助免疫治疗。 的 对照组将是干扰素α 2b（IFN α-2b），最近 已经被FDA批准了。 因为PMCV的毒性更低 比IFN α-2b，疫苗将是优选的佐剂，如果它 临床疗效证明与IFN α-2b相当。 2. 为了确定新的免疫学和分子标记物是否可以 用于检测亚临床转移性黑色素瘤并定量反应 辅助治疗。 我们假设这些新技术可以用于 作为预测辅助治疗结局的分层因素 对于没有临床证据的黑色素瘤患者， 手术 3. 确定最佳影响临床的免疫反应 入组III期试验的PMCV接受者的结局。 我们的目标是 开发一种免疫反应模型， 监测黑色素瘤患者的疫苗治疗。 4. 开展一系列试点研究（第I/II阶段），以确定 针对肿瘤相关抗原的免疫应答可以通过以下方式增强 将PMCV免疫疗法与在黑色素瘤中具有活性的细胞因子相结合 (e.g., IFN α-2b）或作为有效佐剂用于诱导 肿瘤排斥反应的动物模型。

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.