Hassan Raffit, Ho Mitchell
Solid Tumor Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-4264, USA.
Eur J Cancer. 2008 Jan;44(1):46-53. doi: 10.1016/j.ejca.2007.08.028. Epub 2007 Oct 22.
Mesothelin is a tumour differentiation antigen that is normally present on the mesothelial cells lining the pleura, peritoneum and pericardium. It is, however, highly expressed in several human cancers including malignant mesothelioma, pancreatic, ovarian and lung adenocarcinoma. The normal biologic function of mesothelin is unknown but recent studies have shown that it binds to CA-125 and may play a role in the peritoneal spread of ovarian cancer. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy. Three mesothelin targeted agents are in various stages of clinical evaluation in patients. These include SS1P (CAT-5001) a recombinant immunotoxin targeting mesothelin, MORAb-009 a chimeric anti-mesothelin monoclonal antibody and CRS-207 a live-attenuated Listeria monocytogenes vector encoding human mesothelin. These ongoing clinical trials will help define the utility of mesothelin as a target for cancer therapy.
间皮素是一种肿瘤分化抗原,正常情况下存在于胸膜、腹膜和心包膜的间皮细胞上。然而,它在包括恶性间皮瘤、胰腺癌、卵巢癌和肺腺癌在内的多种人类癌症中高度表达。间皮素的正常生物学功能尚不清楚,但最近的研究表明,它与CA-125结合,可能在卵巢癌的腹膜扩散中起作用。间皮素在正常组织中表达有限,而在许多癌症中高表达,这使其成为癌症治疗的一个有吸引力的候选靶点。三种靶向间皮素的药物正处于对患者进行临床评估的不同阶段。这些药物包括SS1P(CAT-5001),一种靶向间皮素的重组免疫毒素;MORAb-009,一种嵌合抗间皮素单克隆抗体;以及CRS-207,一种编码人源间皮素的减毒活单核细胞增生李斯特菌载体。这些正在进行的临床试验将有助于确定间皮素作为癌症治疗靶点的效用。