Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12
Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12
复制标题
单克隆抗体 CH12 对表达 S492R EGFR 的结直肠癌的生长抑制
DOI：
10.1007/s11684-019-0682-z
复制
发表时间：
2019
影响因子：
8.1
通讯作者：
Jiang Hua
中科院分区：
文献类型：
--
作者：
Dong Qiongna;Shi Bizhi;Zhou Min;Gao Huiping;Luo Xiaoying;Li Zonghai;Jiang Hua
结直肠癌（colorectal cancer，CRC）是消化道常见的恶性肿瘤，30%-85%的CRC表达表皮生长因子受体（epidermal growth factor receptor，EGFRs）。最近，使用西妥昔单抗（也称为C225，一种抗EGFR单克隆抗体）治疗CRC已被证明会导致EGFR中的S492R突变。然而，对S492R EGFR的生物学功能知之甚少。因此，我们试图阐明其在CRC细胞中的生物学功能，并探索针对这种突变形式的新治疗策略。我们的研究表明，EGFR和S492R EGFR在体外和体内促进CRC细胞的生长，并且特异性识别EGFR肿瘤特异性表位的单克隆抗体CH 12可以有效地结合S492R EGFR。此外，与mAb C225相比，mAb CH12显示出显著更强的生长抑制活性，并对携带S492R EGFR的CRC细胞诱导更有效的抗体依赖性细胞毒性作用。CH12单抗对S492 R EGFR突变的结直肠癌移植瘤的生长有明显的抑制作用。因此，mAb CH12可能是治疗携带S492R EGFR突变的CRC患者的有希望的治疗剂。
Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and 30%–85% of CRCs express epidermal growth factor receptors (EGFRs). Recently, treatments using cetuximab, also named C225, an anti-EGFR monoclonal antibody, for CRC have been demonstrated to cause an S492R mutation in EGFR. However, little is known about the biological function of S492R EGFR. Therefore, we attempted to elucidate its biological function in CRC cells and explore new treatment strategies for this mutant form. Our study indicated that EGFR and S492R EGFR accelerate the growth of CRC cellsin vitroandin vivoand monoclonal antibody CH12, which specifically recognizes an EGFR tumor-specific epitope, can bind efficiently to S492R EGFR. Furthermore, mAb CH12 showed significantly stronger growth suppression activities and induced a more potent antibody-dependent cellular cytotoxicity effect on CRC cells bearing S492R EGFR than mAb C225. mAb CH12 obviously suppressed the growth of CRC xenografts with S492R EGFR mutationsin vivo. Thus, mAb CH12 may be a promising therapeutic agent in treating patients with CRC bearing an S492R EGFR mutation.