Antitumor efficacy of bispecific antibody mAb04-MICA to human leukemia cell K562 in vitro and in vivo
10.11665/j.issn.1000 -5048.20180117
- VernacularTitle: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
- Author:
Xiaodian DU
1
;
Fumou SUN
;
Minne YUAN
;
Fei WANG
;
Yali LIU
;
Pengzhao SHANG
;
Min WANG
;
Juan ZHANG
Author Information
1. 中国药科大学生命科学与技术学院抗体工程实验室
- Keywords:
bispecific antibody;
VEGFR2;
MICA;
immune surveillance;
leukemia
- From:
Journal of China Pharmaceutical University
2018;49(1):117-124
- CountryChina
- Language:Chinese
-
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.
