PHASE II TRIAL OF HU1418-IL2 (EMD 273063) IN SUBJECTS WITH ADVANCED MELANOMA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究正在测试一种基因工程融合蛋白EMD 273063，用于治疗晚期黑色素瘤患者。我们预计将有14-30名患者参加这项试验。这项试验的目的是评估EMD 273063在晚期黑色素瘤患者中是否具有抗肿瘤活性。EMD 273063是一种免疫细胞因子。这种化合物是通过将两个单独的抗癌分子连接在一起而产生的，是实验性的。EMD 273063的组成成分是人源化的14.18单抗(hu14.18抗体)和白介素2(IL2)。IL2分子是包括黑色素瘤在内的一些癌症的标准治疗形式。白介素2激活免疫细胞。研究表明，虽然IL2治疗可以缩小大约16%的晚期黑色素瘤患者的黑色素瘤，但肿瘤通常会复发。Hu14.18分子是一种人源化的单抗，它与黑色素瘤细胞上发现的GD2分子(结合位点)结合。14.18抗体优先与肿瘤细胞结合(与正常组织相比，与癌细胞结合的机会更大)，但单独使用时，并不能很好地激活免疫系统来摧毁肿瘤。从理论上讲，EMD 273063的hu14.18部分将把IL2直接引向肿瘤细胞，在那里IL2可以激活免疫细胞杀死肿瘤细胞。虽然这种类型的反应已经在实验室动物身上观察到，但还不知道这种分子是否会在黑色素瘤患者中具有同样的抗肿瘤活性。这项研究将确定该疗法对黑色素瘤患者的免疫效果和抗肿瘤效果。

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 is testing a genetically engineered fusion protein EMD 273063 for the treatment of patients with advanced melanoma. We expect to enter 14-30 patients into this trial. The purpose of this trial is to evaluate whether EMD 273063 has antitumor activity in patients with advanced melanoma. EMD 273063 is an immunocytokine. This compound has been created by linking two separate anticancer molecules together and is experimental. The components of EMD 273063 are the humanized 14.18 monoclonal antibody (hu14.18 antibody) and interleukin-2 (IL2). The IL2 molecule is a standard form of treatment for some cancers, including melanoma. Interleukin-2 activates immune cells. Studies have shown that while IL2 treatment may shrink melanomas in approximately 16% of individuals with advanced melanoma, the tumors generally grow back. The hu14.18 molecule is a humanized monoclonal antibody that binds to the GD2 molecules (binding sites) found on melanoma cells. The 14.18 antibody binds preferentially to tumor cells (has a greater chance of binding to cancer cells than to normal tissues), but when used alone, doesn't activate the immune system to destroy tumor very well. In theory, the hu14.18 portion of EMD 273063 will lead the IL2 directly to the tumor cells, where IL2 can activate immune cells to kill the tumor cells. Though this type of reaction has been observed in laboratory animals, it is not known if this molecule will have the same antitumor activity in melanoma patients. This study will determine the immune effects and antitumor effects of this treatment for melanoma patients.