Discovery of mesothelin and exploiting it as a target for immunotherapy.
Discovery of mesothelin and exploiting it as a target for immunotherapy.
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DOI：
10.1158/0008-5472.can-14-0337
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发表时间：
2014-06-01
期刊：
影响因子：
11.2
通讯作者：
Hassan R
中科院分区：
文献类型：
--
作者：
Pastan I;Hassan R
我们最近报道了一种靶向间皮素的免疫毒素在广泛治疗的难治性间皮瘤患者中产生了持久的主要肿瘤消退。这些前所未有的肿瘤反应促使我们回顾间皮素是如何被发现的，以及导致这些肿瘤反应的进展。这篇综述并不全面，但主要集中在过去20年来的主要发展，因为间皮素首次在我们的实验室确定。间皮素是一种细胞表面糖蛋白，其在正常人体组织中的表达仅限于间皮细胞。由于它在许多实体瘤中高度表达，因此它是一个有吸引力的免疫治疗靶点。目前在临床试验中的基于抗体的疗法包括免疫毒素、嵌合单克隆抗体和抗体药物缀合物。此外，间皮素肿瘤疫苗和间皮素-CAR正在临床上进行评估。抗间皮素免疫毒素SS 1 P是第一个进入临床的间皮素靶向治疗，其使用表明间皮素靶向治疗在患者中是安全的。更重要的是，我们最近的工作表明，SS 1 P与喷司他丁和环磷酰胺联合使用可以使晚期间皮瘤患者的肿瘤持久消退，并开辟了这种方法可以使许多常见癌症患者受益的可能性。
We have recently reported that an immunotoxin targeting mesothelin produced durable major tumor regressions in patients with extensive treatment refractory mesothelioma. These unprecedented tumor responses have prompted us to review how mesothelin was discovered and the advances that led to these tumor responses. This review is not comprehensive but focuses on major developments over the past 20 years since mesothelin was first identified in our laboratory. Mesothelin is a cell-surface glycoprotein whose expression in normal human tissues is restricted to mesothelial cells. Because it is highly expressed by many solid tumors it is an attractive immunotherapy target. Antibody based therapies currently in clinical trials include an immunotoxin, a chimeric monoclonal antibody and an antibody drug conjugate. In addition, a mesothelin tumor vaccine and a mesothelin-CAR are being evaluated in the clinic. SS1P, an anti-mesothelin immunotoxin was the first mesothelin directed therapy to enter the clinic and its use showed that mesothelin targeted therapy was safe in patients. More importantly our recent work has shown that SS1P in combination with pentostatin and cyclophosphamide can result in durable tumor regression in patients with advanced mesothelioma and opens up the possibility that such an approach can benefit patients with many common cancers.