Antitumor efficacy of bispecific antibody mAb04-MICA to human leukemia cell K562 in vitro and in vivo / 中国药科大学学报
Journal of China Pharmaceutical University
; (6): 117-124, 2018.
Article
em Zh
| WPRIM
| ID: wpr-704331
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WPRO
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.
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Índice:
WPRIM
Idioma:
Zh
Revista:
Journal of China Pharmaceutical University
Ano de publicação:
2018
Tipo de documento:
Article