In vitro application of anti-CD47 monoclonal antibody for targeted therapy of ovarian cancer

Baohui Ju, Yuting Huang, Jing Tian, Hui Feng, Linping Hu, Weiping Yuan, Quan Hao

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    4 Scopus citations

    Abstract

    Objective: CD47 is highly expressed on human ovarian cancer cell surface and is a ligand for signal-regulatory protein alpha (SIRPα). The CD47-SIRPα pathway has been found to negatively regulate macrophage phagocytosis. We hypothesize that this pathway enables ovarian cancer cells to escape during tumor immunosurveillance. CD47 is highly expressed in various malignant diseases. This study aimed to explore whether CD47 can serve as a potential therapeutic target for ovarian cancer. Methods: Tissue samples were obtained from 39 epithelial ovarian cancer patients. Six patients underwent other operations during which normal ovarian tissue samples were obtained. The expression of CD47 in the ovary cancer cell line SKOV-3 in normal ovarian tissues and ovarian cancer cells were analyzed by quantitative fluorescence-activated cell sorting. Macrophages and CFSE-labeled SKOV-3 cells were co-cultured with the indicated antibodies through in vitro phagocytosis assay, and phagocytic index was calculated. Results: Flow cytometry showed that the expression levels of CD47 in the ovarian cancer cell line SKOV-3 and ovarian cancer cells were significantly higher than in normal ovarian epithelial cells (P<0.01). This result is associated with the grade of differentiation of the disease (P<0.05). Blocking a monoclonal antibody against CD47 promotes in vitro phagocytosis of ovarian cancer cells by macrophages. The phagocytic index of the experimental groups (1, 5, 10, and 20 μg/ml) increased significantly (P<0.01) compared with the control group. The occurrence was found to be concentration-dependent (P<0.01). Statistical analysis showed that the maximum phagocytic index was found in the 10 μg/ml concentration group; the same was observed in the 20 μg/ml group. However, no significant difference was found between the two groups (P>0.05). Conclusion: CD47 is expressed in epithelial ovarian cancer cells at a higher level compared with normal ovarian cells. The level of expression is associated with tissue differentiation grade. Our study indicates that the anti-CD47 monoclonal antibody can significantly promote in vitro phagocytosis, indicating that the anti-CD47 monoclonal antibody might be a potential target in targeted cancer therapy.

    Original languageEnglish (US)
    Pages (from-to)440-443
    Number of pages4
    JournalChinese Journal of Clinical Oncology
    Volume40
    Issue number8
    DOIs
    StatePublished - Apr 30 2013

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    Keywords

    • CD47
    • Macrophage
    • Monoclonal antibody
    • Ovarian cancer
    • Targeting therapy

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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