文章：

一种靶向SAIL的新型抗体-药物偶联物，用于治疗血液系统恶性肿瘤

A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies

原文发布日期：2015-05-29

DOI: 10.1038/bcj.2015.39

类型: Original Article

开放获取: 是

英文摘要：

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin’s lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody–drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs.

摘要翻译： 

尽管若干新型疗法已改善血液恶性肿瘤的治疗结局，但急性髓系白血病、多发性骨髓瘤和非霍奇金淋巴瘤领域仍存在未满足的临床需求。本文通过蛋白质组学鉴定出一种新型癌症靶点SAIL（白血病表面抗原），该靶点在急性髓系白血病、多发性骨髓瘤、慢性淋巴细胞白血病、弥漫性大B细胞淋巴瘤和滤泡性淋巴瘤中均有表达。虽然SAIL在慢性淋巴细胞白血病、急性髓系白血病、多发性骨髓瘤、弥漫性大B细胞淋巴瘤及滤泡性淋巴瘤患者样本中广泛表达，但在癌细胞系中的表达主要局限于急性髓系白血病来源的细胞。我们评估了与单甲基奥瑞他汀F偶联的SAIL单克隆抗体7-1C和67-7A的抗肿瘤活性。经内化后，抗SAIL抗体-药物偶联物在体外对急性髓系白血病细胞系显示出亚纳摩尔级的半数抑制浓度。在使用急性髓系白血病细胞系异种移植模型的药理学研究中，抗SAIL抗体-药物偶联物可实现显著的肿瘤生长抑制。该靶点在正常组织中表达受限、在多种血液癌症中高表达的特性及临床前观察到的活性，为SAIL靶向抗体-药物偶联物的临床开发提供了支持。

原文链接：

A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies