title: VEGFR2-targeted fusion antibody improved NK cell-mediated immunosurveillance against K562 cells.
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.
authors.affiliation: 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.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Ren
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: 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.
authors.forename: Youfu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Menghuai
authors.initials: M
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Mingying
authors.initials: M
authors.lastname: Tang
authors.affiliation: 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.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D015550:Cell Degranulation; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007157:Immunologic Surveillance; D056747:Immunomodulation; D007167:Immunotherapy / Q000379:methods*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D015398:Signal Transduction; D019139:Tumor Escape; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000074322:Antineoplastic Agents, Immunological; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011993:Recombinant Fusion Proteins; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Antibody fusion protein; Immunosurveillance; MHC class I polypeptide-related sequence A (MICA); Vascular endothelial growth factor receptor 2 (VEGFR2)