Antitumor efficacy of bispecific antibody mAb04-MICA to human leukemia cell K562<i> in vitro </i>and <i>in vivo</i>

DU Xiaodian; SUN Fumou; YUAN Minne; WANG Fei; LIU Yali; SHANG Pengzhao; WANG Min; ZHANG Juan

doi:10.11665/j.issn.1000-5048.20180117

Journal of China Pharmaceutical University > 2018 > 49(1): 117-124. > DOI: 10.11665/j.issn.1000-5048.20180117

DU Xiaodian, SUN Fumou, YUAN Minne, WANG Fei, LIU Yali, SHANG Pengzhao, WANG Min, ZHANG Juan. Antitumor efficacy of bispecific antibody mAb04-MICA to human leukemia cell K562 in vitro and in vivo[J]. Journal of China Pharmaceutical University, 2018, 49(1): 117-124. DOI: 10.11665/j.issn.1000-5048.20180117

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Antitumor efficacy of bispecific antibody mAb04-MICA to human leukemia cell K562 in vitro and in vivo

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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 had 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 immunohistochemistry. The results indicated that mAb04-MICA could target to VEGFR2 and NKG2D, and inhibit K562 proliferation 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.
- bispecific antibody,
- VEGFR2,
- MICA,
- immune surveillance,
- leukemia

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Antitumor efficacy of bispecific antibody mAb04-MICA to human leukemia cell K562 in vitro and in vivo

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