Mesothelin Immunotherapy for Cancer: Ready for Prime Time?
Mesothelin Immunotherapy for Cancer: Ready for Prime Time?
复制标题
DOI：
10.1200/jco.2016.68.3672
复制
发表时间：
2016-12-01
影响因子：
45.3
通讯作者：
Pastan, Ira
中科院分区：
文献类型：
--
作者：
Hassan, Raffit;Thomas, Anish;Pastan, Ira
间皮素是一种肿瘤抗原，在许多人类癌症中高度表达，包括恶性间皮瘤以及胰腺癌、卵巢癌和肺腺癌。它是癌症免疫治疗的一个有吸引力的靶点，因为它的正常表达仅限于间皮细胞，而间皮细胞是不稳定的。针对间皮素的几种基于抗体的治疗剂以及疫苗和T细胞疗法正在进行临床评估。这些包括抗间皮素免疫毒素（SS 1 P、RG 7787/LMB-100）、嵌合抗间皮素抗体（amatuximab）、间皮素定向抗体药物偶联物（anetumab ravtansine、DMOT 4039 A、BMS-986148）、表达间皮素的减毒活单核细胞增生李斯特菌（CRS-207、JNJ-64041757）和嵌合抗原受体T细胞疗法。两种抗间皮素药物目前正在进行恶性间皮瘤的多中心临床注册试验：一线治疗为amatuximab，二线治疗为anetumab ravtansine。CRS-207作为增强剂并与免疫检查点抑制剂联合用于胰腺癌的II期随机临床试验即将完成。这些正在进行的研究将确定间皮素免疫疗法用于治疗癌症的效用。(C)2016年美国临床肿瘤学会
Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies. Two antimesothelin agents are currently in multicenter clinical registration trials for malignant mesothelioma: amatuximab in the first-line setting and anetumab ravtansine as second-line therapy. Phase II randomized clinical trials of CRS-207 as a boosting agent and in combination with immune checkpoint inhibition for pancreatic cancer are nearing completion. These ongoing studies will define the utility of mesothelin immunotherapy for treating cancer. (C) 2016 by American Society of Clinical Oncology