Oncotarget

Research Papers:

VEGFR2 targeted antibody fused with MICA stimulates NKG2D mediated immunosurveillance and exhibits potent anti-tumor activity against breast cancer

Wei Xei, Fang Liu, Youfu Wang, Xueyan Ren, Tong Wang, Zhiguo Chen, Mingying Tang, Fumou Sun, Zhaoting Li, Min Wang and Juan Zhang _

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Oncotarget. 2016; 7:16445-16461. https://doi.org/10.18632/oncotarget.7501

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Abstract

Wei Xie1,*, Fang Liu1,*, Youfu Wang1, Xueyan Ren1, Tong Wang1, Zhiguo Chen1, Mingying Tang1, Fumou Sun1, Zhaoting Li1, Min Wang1, Juan Zhang1

1State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China

*These authors should be considered as joint first authors

Correspondence to:

Juan Zhang, e-mail: juancpu@126.com

Min Wang, e-mail: minwang@cpu.edu.cn

Keywords: antibody fusion protein, VEGFR2, MICA, anti-angiogenesis, immunosurveillance

Received: August 25, 2015    Accepted: January 29, 2016    Published: February 19, 2016

ABSTRACT

Binding of MHC class I-related chain molecules A and B (MICA/B) to the natural killer (NK) cell receptor NK group 2, member D (NKG2D) is thought critical for activating NK-mediated immunosurveillance. Angiogenesis is important for tumor growth and interfering with angiogenesis using the fully human IgG1 anti-VEGFR2 (vascular endothelial growth factor receptor 2) antibody (mAb04) can be effective in treating malignancy. In an effort to make mAb04 more effective we have generated a novel antibody fusion protein (mAb04-MICA) consisting of mAb04 and MICA. We found that mAb04-MICA maintained the anti-angiogenic and antineoplastic activities of mAb04, and also enhanced immunosurveillance activated by the NKG2D pathway. Moreover, in human breast tumor-bearing nude mice, mAb04-MICA demonstrated superior anti-tumor efficacy compared to combination therapy of mAb04 + Docetaxel or Avastin + Docetaxel, highlighting the immunostimulatory effect of MICA. In conclusion, mAb04-MICA provided new inspiration for anti-tumor treatment and had prospects for clinical application.


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