Original Article

Cancer Immunology, Immunotherapy

, Volume 61, Issue 10, pp 1735-1743

First online:

Expression of CD40 and growth-inhibitory activity of CD40 agonist in ovarian carcinoma cells

  • Yan ZhouAffiliated withState Key Laboratory of Biotherapy, West China Hospital, Sichuan University
  • , Jing HeAffiliated withState Key Laboratory of Biotherapy, West China Hospital, Sichuan University
  • , Lan-tu GouAffiliated withState Key Laboratory of Biotherapy, West China Hospital, Sichuan University
  • , Bo MuAffiliated withState Key Laboratory of Biotherapy, West China Hospital, Sichuan University
  • , Wei-chan LiaoAffiliated withState Key Laboratory of Biotherapy, West China Hospital, Sichuan University
  • , Cong MaAffiliated withState Key Laboratory of Biotherapy, West China Hospital, Sichuan University
  • , Ping TangAffiliated withState Key Laboratory of Biotherapy, West China Hospital, Sichuan University
  • , Shi-jie ZhouAffiliated withState Key Laboratory of Biotherapy, West China Hospital, Sichuan University
  • , Yong-jun ZhouAffiliated withState Key Laboratory of Biotherapy, West China Hospital, Sichuan University
    • , Jin-liang YangAffiliated withState Key Laboratory of Biotherapy, West China Hospital, Sichuan University Email author 

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Abstract

The CD40 receptor is a member of the tumour necrosis factor receptor family and is widely expressed on various cell types. The antitumour activity of CD40 agonist antibody has been observed in B-cell-derived malignancies, but its activity on ovarian cancer remains unclear. However, in this paper, we first confirmed that the anti-CD40 agonist antibody could inhibit the growth of ovarian cancer cells and induce apoptosis. This study investigated the expression of CD40 by ovarian carcinoma tissues and cell lines, at the same time, we evaluated the effect of a recombinant soluble human CD40L (rshCD40L) and an anti-CD40 agonist antibody on cell growth and apoptosis. Flow cytometry and immunohistochemistry assay demonstrated that CD40 was expressed on ovarian carcinoma cell lines and primary ovarian carcinoma cells derived from ascites, as well as on ovarian carcinoma tissues. The growth inhibition of rshCD40L and the anti-CD40 agonist antibody on ovarian carcinoma cells was examined by MTT assay, and the proportion of apoptotic tumour cells was analysed by flow cytometry and Hoechst staining. Our study showed that CD40 was expressed on all ovarian carcinoma cell lines and was examined in 86.2% (162/188) of ovarian cancer tissue samples, but not in normal ovarian tissues (n = 20). Treatment with rshCD40L or anti-CD40 agonist antibody significantly inhibited ovarian carcinoma cell growth and induced apoptosis. Theses results suggest that CD40 is expressed on ovarian carcinoma cells, moreover, that rshCD40L and anti-CD40 agonist antibody have therapeutic potential to inhibit human ovarian cancer growth.

Keywords

Ovarian carcinoma CD40L CD40 Agonist antibody