• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
DU Xiaodian, SUN Fumou, YUAN Minne, WANG Fei, LIU Yali, SHANG Pengzhao, WANG Min, ZHANG Juan. Antitumor efficacy of bispecific antibody mAb04-MICA to human leukemia cell K562 in vitro and in vivo[J]. Journal of China Pharmaceutical University, 2018, 49(1): 117-124. DOI: 10.11665/j.issn.1000-5048.20180117
Citation: DU Xiaodian, SUN Fumou, YUAN Minne, WANG Fei, LIU Yali, SHANG Pengzhao, WANG Min, ZHANG Juan. Antitumor efficacy of bispecific antibody mAb04-MICA to human leukemia cell K562 in vitro and in vivo[J]. Journal of China Pharmaceutical University, 2018, 49(1): 117-124. DOI: 10.11665/j.issn.1000-5048.20180117
shu

Antitumor efficacy of bispecific antibody mAb04-MICA to human leukemia cell K562 in vitro and in vivo

More Information
    Graphical Abstract
    • Abstract
  • This study aimed to investigate the efficacy of a bispecific antibody mAb04-MICA on human leukemia cell K562 both in vitro and vivo. mAb04-MICA was previously found to posses excellent anti-angiogenic activity, and had the ability to recruit immune surveillance in tumor microenvironment. In this study, the affinity of mAb04-MICA to VEGFR2 and NKG2D was identified by ELISA. CCK8 was used to detect the effect of mAb04-MICA on K562 proliferation. The cross reactivity of mAb04-MICA to murine VEGFR2 was determined by flow cytometry assay. To evaluate the antitumor activity of mAb04-MICA, tumor volume, tumor weight and the survival of K562 tumor-bearing nude mice were analyzed. The anti-angiogenic activity was determined by immunohistochemistry. The results indicated that mAb04-MICA could target to VEGFR2 and NKG2D, and inhibit K562 proliferation specifically. Besides, mAb04-MICA showed high binding capacity to murine VEGFR2. The bispecific antibody exhibited superior antitumor efficacy to the maternal monoclonal antibody and prolonged the survival of tumor-bearing mice. The expression of Ki-67, p-VEGFR2, VEGF and CD34 in mAb04-MICA treated group was significantly reduced. The results indicated that mAb04-MICA could attenuate the phosphorylation of VEGFR2 and impair angiogenesis of the tumor microenviroment. Therefore, mAb04-MICA could be further developed as a potential tumor targeted immunotherapeutic agent for leukemia.
    • FullText(HTML)
    • References (21)
  • [1]
    Ferrara N,Kerbel RS.Angiogenesis as a therapeutic target[J].Nature,2005,438(7070):967-974.
    [2]
    Carmeliet P,Jain RK.Molecular mechanisms and clinical applications of angiogenesis[J].Nature,2011,473(7347):298-307.
    [3]
    Jr RR.Vascular endothelial growth factor(VEGF)signaling in tumor progression[J].Crit Rev Oncol Hematol,2007,62(3):179-213.
    [4]
    Musumeci F,Radi M,Brullo C,et al.Vascular endothelial growth factor(VEGF)receptors:drugs and new inhibitors[J].J Med Chem,2012,55(24):10797-10822.
    [5]
    Xu WW,Li B,Lam AK,et al.Targeting VEGFR1- and VEGFR2-expressing non-tumor cells is essential for esophageal cancer therapy[J].Oncotarget,2015,6(3):1790-1805.
    [6]
    Fuchs CS,Tabernero J,Tomášek J,et al.Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab[J].Br J Cancer,2016,115(8):974-982.
    [7]
    Fuchs CS,Tomasek J,Yong CJ,et al.Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma(REGARD):an international,randomised,multicentre,placebo-controlled,phase 3 trial[J].Lancet,2014,383(9911):31-39.
    [8]
    Saif MW,Elfiky A,Salem RR.Gastrointestinal perforation due to bevacizumab in colorectal cancer[J].Ann Surg Oncol,2007,14(6):1860-1869.
    [9]
    Kappers MH,Smedts FM,Horn T,et al.The vascular endothelial growth factor receptor inhibitor sunitinib causes a preeclampsia-like syndrome with activation of the endothelin system[J].Hypertension,2011,58(2):295-302.
    [10]
    Cho HM,Rosenblatt JD,Tolba K,et al.Delivery of NKG2D ligand using an anti-HER2 antibody-NKG2D ligand fusion protein results in an enhanced innate and adaptive antitumor response[J].Cancer Res,2010,70(24):10121-10130.
    [11]
    Veluchamy JP, Heeren AM, Spanholtz J, et al. High-efficiency lysis of cervical cancer by allogeneic NK cells derived from umbilical cord progenitors is independent of HLA status[J].Cancer Immunol Immunother,2017,66(1):51.
    [12]
    Lopez-Soto A,Huergo-Zapico L,Acebes-Huerta A,et al.NKG2D signaling in cancer immunosurveillance[J].Int J Cancer,2015,136(8):1741-1750.
    [13]
    Isernhagen A, Malzahn D, Viktorova E, et al. The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation[J].EMBO Mol Med,2015,7(11):1480-1502.
    [14]
    Wu JD,Atteridge CL,Wang X,et al.Obstructing shedding of the immunostimulatory MHC class I chain-related gene B prevents tumor formation[J].Clin Cancer Res,2009,15(2):632-640.
    [15]
    Xie W,Fang L,Wang Y,et al.VEGFR2 targeted antibody fused with MICA stimulates NKG2D mediated immunosurveillance and exhibits potent anti-tumor activity against breast cancer[J].Oncotarget,2016,7(13):16445-16461.
    [16]
    Ren X,Xie W,Wang Y,et al.VEGFR2-targeted fusion antibody improved NK cell-mediated immunosurveillance against K562 cells[J].Immunol Res,2016,64(4):1060-1070.
    [17]
    Zhou YJ,Dou RK,Bi ZF,et al.Promotion of apoptosis in leukemia K562 cells by natural plant-derived antimicrobial solution(PAMs)[J].J China Pharma Univ(中国药科大学学报),2015,46(6):712-718.
    [18]
    Shi L,Zhang J,Wu P,et al.Discovery and identification of potential biomarkers of pediatric acute lymphoblastic leukemia[J].Proteome Sci,2009,7(1):7.
    [19]
    Xie W,Li D,Zhang J,et al.Generation and characterization of a novel human IgG1 antibody against vascular endothelial growth factor receptor 2[J].Cancer Immunol Immunother,2014,63(9):877-888.
    [20]
    Acheampong DO,Tang M,Wang Y,et al.A novel fusion antibody exhibits antiangiogenic activity and stimulates NK cell-mediated immune surveillance through fused NKG2D ligand[J].J Immunother,2017,40(3):94-103.
    [21]
    Wang T,Sun F,Xie W,et al.A bispecific protein rG7S-MICA recruits natural killer cells and enhances NKG2D-mediated immunosurveillance against hepatocellular carcinoma[J].Cancer Lett,2016,372(2):166-178.
    • Related Articles

  • Related Articles

    [1]ZHAO Pengbo, ZHU Ying, YIN Lifang, XIN Xiaofei. Progress of gene-mediated precision immunotherapy in the treatment of acute myeloid leukemia[J]. Journal of China Pharmaceutical University, 2024, 55(1): 53-62. DOI: 10.11665/j.issn.1000-5048.2023112703
    [2]CHEN Jiao, WANG Xiaodong, JIA Yongqian. Construction and identification of FLT3-ITD/ FIV expression vector and acute myelogenous leukemia cell lines[J]. Journal of China Pharmaceutical University, 2017, 48(6): 727-732. DOI: 10.11665/j.issn.1000-5048.20170615
    [3]ZHOU Yijie, DOU Rongkun, BI Zhenfei, YANG Yalan, LIU Zongying, WU Yiran, QIU Jinyi, XIANGFEI Danzhou, MAO Canquan. Promotion of apoptosis in leukemia K562 cells by natural plant-derived antimicrobial solution(PAMs)[J]. Journal of China Pharmaceutical University, 2015, 46(6): 712-718. DOI: 10.11665/j.issn.1000-5048.20150613
    [4]LI Tonghui, GUO Hao, LU Tao, WANG Yue, LU Shuai, TANG Weifang. Advances in the research of FLT3 inhibitors for acute myeloid leukemia[J]. Journal of China Pharmaceutical University, 2015, 46(2): 153-161. DOI: 10.11665/j.issn.1000-5048.20150203
    [5]XIE Weiquan, DAI Wen, WANG Shuzhen, CHEN Yijun. A novel peptide and its mechanism overcoming imatinib-resistance chronic myeloid leukemia[J]. Journal of China Pharmaceutical University, 2014, 45(3): 368-372. DOI: 10.11665/j.issn.1000-5048.20140321
    [6]WANG Yu, ZHAO Li, MIAO Hanchi, LI Zhiyu, GUO Qinglong. Apoptosis induction of oroxylin A in human chronic myelogenous leukemia cell line K562[J]. Journal of China Pharmaceutical University, 2014, 45(2): 232-236. DOI: 10.11665/j.issn.1000-5048.20140218
    [7]DENG Lin, ZHANG Rui, LI Chen, XING Ying-ying, XI Tao. Mechanism of the differentiation of human leukemia cell line HL-60 induced by ursolic acid[J]. Journal of China Pharmaceutical University, 2012, 43(4): 361-365.
    [8]ZHANG Ting, SHEN Jing, REN Tian-nian, LIU Kun-mei, XI Tao. Ursolic acid-induced differentiation of human monocytic leukemia cell line THP-1[J]. Journal of China Pharmaceutical University, 2010, 41(6): 572-576.
    [9]FENG Lan-ying, HUANG Wen-ye. Expression and regulation of Bim protein in chronic myelogenous leukemia[J]. Journal of China Pharmaceutical University, 2009, 40(6): 571-575.

Catalog

    Get Citation
    PDF
    XML
    Article views (965) PDF downloads (1588) Cited by()
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Copyright © Journal of China Pharmaceutical University苏ICP备12050101号-2

    Address：24 Tongjia Lane, Nanjing City, Jiangsu Province （210009）Tel: 025-83271566E-mail: xuebao@cpu.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    Total visits：301713

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return