中国药科大学学报2018，Vol.49Issue(1)：117-124,8.DOI:10.11665/j.issn.1000 -5048.20180117
双特异性抗体mAb04-MICA对人白血病细胞K562的体内外抗肿瘤活性
Antitumor efficacy of bispecific antibody mAb04-MICA to human leukemia cell K562 in vitro and in vivo
摘要
Abstract
This study aimed to investigate the efficacy of a bispecific antibody mAb04-MICA on human leukemia cell K562 both in vitro and vivo. mAb04-MICA was previously found to posses excellent anti-angiogenic activity, and have the ability to recruit immune surveillance in tumor microenvironment. In this study, the affinity of mAb04-MICA to VEGFR2 and NKG2D was identified by ELISA. CCK8 was used to detect the effect of mAb04-MICA on K562 proliferation. The cross reactivity of mAb04-MICA to murine VEGFR2 was determined by flow cytometry assay. To evaluate the antitumor activity of mAb04-MICA,tumor volume,tumor weight and the survival of K562 tumor-bearing nude mice were analyzed. The anti-angiogenic activity was determined by immunohisto-chemistry. The results indicated that mAb04-MICA could target to VEGFR2 and NKG2D,and inhibit K562 pro-liferation specifically. Besides,mAb04-MICA showed high binding capacity to murine VEGFR2. The bispecific antibody exhibited superior antitumor efficacy to the maternal monoclonal antibody and prolonged the survival of tumor-bearing mice. The expression of Ki-67,p-VEGFR2,VEGF and CD34 in mAb04-MICA treated group was significantly reduced. The results indicated that mAb04-MICA could attenuate the phosphorylation of VEGFR2 and impair angiogenesis of the tumor microenviroment. Therefore,mAb04-MICA could be further developed as a potential tumor targeted immunotherapeutic agent for leukemia.关键词
双特异性抗体/血管内皮生长因子受体2/MHC-I相关抗原分子A/免疫监视/白血病Key words
bispecific antibody/VEGFR2/MICA/immune surveillance/leukemia分类
生物科学引用本文复制引用
杜晓典,孙福谋,袁敏讷,王斐,刘雅利,尚鹏钊,王旻,张娟..双特异性抗体mAb04-MICA对人白血病细胞K562的体内外抗肿瘤活性[J].中国药科大学学报,2018,49(1):117-124,8.基金项目
国家自然科学基金资助项目(No.81473125) （No.81473125）
江苏省自然科学基金资助项目(No.BK20161459) （No.BK20161459）
江苏高校“青蓝工程”资助项目(2014) （2014）
大学生创新创业训练计划资助项目(No.201710316032X)This study was supported by the National Natural Science Foundation of China ( No. 81473125) （No.201710316032X）
the Natural Science Foundation of Jiangsu Province ( No. BK20161459) （ No. BK20161459）
the Qinglan Project of Jiangsu Province ( 2014) （ 2014）
and the Undergraduate Innovation and Entrepreneurship Training Program ( No. 201710316032X) （ No. 201710316032X）
