Baldo Paolo, Cecco Sara
Pharmacy Unit, Directorate Department, CRO Aviano-IRCCS National Cancer Institute, Aviano, Italy.
Onco Targets Ther. 2017 Nov 8;10:5337-5353. doi: 10.2147/OTT.S145105. eCollection 2017.
Mesothelin (MSLN) is considered a promising target for cancer therapy. Originally extracted in 1992 after the immunization of mice with a human ovarian cancer (OC) cell line and cloned in 1996, MSLN seems to be involved in cell adhesion and metastasis. MSLN is prevalent in mesothelia tissues but is expressed in several human cancers, such as OC, pancreatic cancer, mesothelioma, and lung cancer. Amatuximab (MORAb-009) is a mouse-human chimeric monoclonal antibody with a selective affinity for MSLN. The principal mechanism of action comprises inhibition of binding of MSLN with the antigen CA125/MUC16. The highest phase of development is actually a Phase II trial (MORAb-009-201, Europe). In this review, we describe the mechanism of action of amatuximab and other MSLN-targeting novel drugs, along with a discussion about the expected efficacy, safety, and toxicity of this promising group of agents and implications for future research and clinical practice.
间皮素(MSLN)被认为是癌症治疗的一个有前景的靶点。1992年在用人类卵巢癌细胞系免疫小鼠后首次提取,并于1996年克隆,MSLN似乎参与细胞黏附和转移。MSLN在间皮组织中普遍存在,但在几种人类癌症中表达,如卵巢癌、胰腺癌、间皮瘤和肺癌。阿马妥昔单抗(MORAb-009)是一种对MSLN具有选择性亲和力的鼠-人嵌合单克隆抗体。主要作用机制包括抑制MSLN与抗原CA125/MUC16的结合。目前最高的研发阶段实际上是一项II期试验(MORAb-009-201,欧洲)。在本综述中,我们描述了阿马妥昔单抗和其他靶向MSLN的新型药物的作用机制,同时讨论了这一有前景的药物组的预期疗效、安全性和毒性,以及对未来研究和临床实践的影响。