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Immunol Res. 2016 Aug;64(4):1060-70. doi: 10.1007/s12026-016-8800-3.

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

Author information

1
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 154#, Tong Jia Xiang 24, Nanjing, 210009, People's Republic of China.
2
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 154#, Tong Jia Xiang 24, Nanjing, 210009, People's Republic of China. minwang@cpu.edu.cn.
3
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 154#, Tong Jia Xiang 24, Nanjing, 210009, People's Republic of China. juancpu@126.com.

Abstract

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.

KEYWORDS:

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

PMID:
27154226
DOI:
10.1007/s12026-016-8800-3
[Indexed for MEDLINE]

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