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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。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。本试验的目的是评估EMD 273063是否对晚期黑色素瘤患者具有抗肿瘤活性。EMD 273063是一种免疫细胞因子。这种化合物是通过将两个独立的抗癌分子连接在一起而产生的，并且是实验性的。EMD 273063的组分是人源化14.18单克隆抗体（hu14.18抗体）和白细胞介素-2（IL 2）。IL 2分子是治疗某些癌症（包括黑色素瘤）的标准形式。IL 2激活免疫细胞。研究表明，虽然IL 2治疗可以缩小约16%的晚期黑色素瘤患者的黑色素瘤，但肿瘤通常会重新生长。hu14.18分子是一种人源化单克隆抗体，可与黑素瘤细胞上发现的GD 2分子（结合位点）结合。14.18抗体优先与肿瘤细胞结合（与癌细胞结合的机会大于与正常组织结合的机会），但单独使用时，不能很好地激活免疫系统来破坏肿瘤。理论上，EMD 273063的hu14.18部分会将IL 2直接导向肿瘤细胞，在那里IL 2可以激活免疫细胞杀死肿瘤细胞。虽然在实验室动物中观察到了这种类型的反应，但尚不清楚这种分子是否会在黑色素瘤患者中具有相同的抗肿瘤活性。本研究将确定这种治疗对黑色素瘤患者的免疫作用和抗肿瘤作用。

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. IL2 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.