VEGFR2-targeted fusion antibody improved NK cell-mediated immunosurveillance against K562 cells
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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.
KeywordsAntibody 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
Fluorescence-activated cell sorter
Fetal bovine serum
Fc gamma receptors
Major histocompatibility complex
MHC class I polypeptide-related sequence A/B
NK group 2-member D
Peripheral blood mononuclear cells
Single-chain fragment variable
Tumor necrosis factor alpha
Vascular endothelial growth factor
Vascular endothelial growth factor receptor 2
Methyl thiazolyl tetrazolium
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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