Immunologic Research

, Volume 64, Issue 4, pp 1060–1070 | Cite as

VEGFR2-targeted fusion antibody improved NK cell-mediated immunosurveillance against K562 cells

  • Xueyan Ren
  • Wei Xie
  • Youfu Wang
  • Menghuai Xu
  • Fang Liu
  • Mingying Tang
  • Chenchen Li
  • Min WangEmail author
  • Juan ZhangEmail author
Original Article


MHC class I polypeptide-related sequence A (MICA), which is normally expressed on cancer cells, activates NK cells via NK group 2-member D pathway. However, some cancer cells escape NK-mediated immune surveillance by shedding membrane MICA causing immune suppression. To address this issue, we designed an antibody-MICA fusion targeting tumor-specific antigen (vascular endothelial growth factor receptor 2, VEGFR2) based on our patented antibody (mAb04) against VEGFR2. In vitro results demonstrate that the fusion antibody retains both the antineoplastic and the immunomodulatory activity of mAb04. Further, we revealed that it enhanced NK-mediated immunosurveillance against K562 cells through increasing degranulation and cytokine production of NK cells. The overall data suggest our new fusion protein provides a promising approach for cancer-targeted immunotherapy and has prospects for potential application of chronic myeloid leukemia.


Antibody fusion protein Vascular endothelial growth factor receptor 2 (VEGFR2) MHC class I polypeptide-related sequence A (MICA) Immunosurveillance 



Antibody-dependent cellular cytotoxicity


American Type Culture Collection


Acute myeloid leukemia


Complement-dependent cytotoxicity


Fluorescence-activated cell sorter


Fetal bovine serum


Fragment crystallizable


Fc gamma receptors


Fluorescein isothiocyanate




Interferon gamma


Major histocompatibility complex


MHC class I polypeptide-related sequence A/B


NK group 2-member D


Peripheral blood mononuclear cells


Propidium iodide


Single-chain fragment variable


Standard deviation


Tumor necrosis factor alpha


UL16-binding protein


Vascular endothelial growth factor


Vascular endothelial growth factor receptor 2


Soluble MICA


Membrane MICA


Methyl thiazolyl tetrazolium


Phosphate-buffered saline


Monoclonal antibody



This project was supported by the National Natural Science Foundation of China (NSFC81102364, NSFC81273425 and NSFC81473125), Specialized Research Fund for the Doctoral Program of Higher Education (20130096110007), Jiangsu Province Qinglan Project (2014) and China Scholarship Council, Graduate Student Innovation Project Funded by Huahai Pharmaceutical Co. (CX13S-009HH) and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Compliance with ethical standards

Conflict of interests

The authors declare no conflict of interests.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Xueyan Ren
    • 1
  • Wei Xie
    • 1
  • Youfu Wang
    • 1
  • Menghuai Xu
    • 1
  • Fang Liu
    • 1
  • Mingying Tang
    • 1
  • Chenchen Li
    • 1
  • Min Wang
    • 1
    Email author
  • Juan Zhang
    • 1
    Email author
  1. 1.State Key Laboratory of Natural Medicines, School of Life Science and TechnologyChina Pharmaceutical UniversityNanjingPeople’s Republic of China

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