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抗体-白细胞介素 2 为基础的免疫疗法的发展与 hu14.18-白细胞介素 2(EMD-273063)在黑色素瘤和神经母细胞瘤。

The development of antibody-IL-2 based immunotherapy with hu14.18-IL2 (EMD-273063) in melanoma and neuroblastoma.

机构信息

The University of Wisconsin-Madison, Departments of Surgery, WI 53792, USA.

出版信息

Expert Opin Investig Drugs. 2009 Jul;18(7):991-1000. doi: 10.1517/13543780903048911.

Abstract

Patients with high risk melanoma and neuroblastoma frequently experience recurrence despite surgical resection and appropriate adjuvant therapies. Immunotherapy with the immunocytokine hu14.18-IL2 (EMD-273063) was developed by means of fusion of two molecules of IL-2 to the monoclonal antibody, 14.18, that recognizes GD2, expressed on the earlier mentioned malignancies. This article will discuss the results of preclinical work using EMD-273063 therapy, including data suggesting that intratumoral therapy may have enhanced antitumor benefit compared with intravenous therapy. Initial clinical trials in adult melanoma and pediatric neuroblastoma have demonstrated acceptable toxicity profiles in dosing that induces immune activation. Preclinical and initial clinical data suggest greater efficacy in the setting of minimal residual disease; therefore, future clinical testing is planned to test the benefit of EMD-273063 in this setting.

摘要

尽管进行了手术切除和适当的辅助治疗,高风险黑色素瘤和神经母细胞瘤患者仍经常复发。免疫细胞因子 hu14.18-IL2(EMD-273063)的免疫疗法是通过将两种 IL-2 分子融合到单克隆抗体 14.18 上来开发的,该抗体识别 GD2,表达在前面提到的恶性肿瘤上。本文将讨论使用 EMD-273063 治疗的临床前工作结果,包括数据表明与静脉内治疗相比,肿瘤内治疗可能具有增强的抗肿瘤益处。在诱导免疫激活的剂量下,成人黑色素瘤和儿科神经母细胞瘤的初步临床试验显示出可接受的毒性特征。临床前和初步临床数据表明,在最小残留疾病的情况下,疗效更大;因此,计划进行未来的临床测试,以测试 EMD-273063 在这种情况下的益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a991/2952306/a765c2086f82/nihms233879f1.jpg

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