Open AccessA SIRPα‐Fc fusion protein enhances the antitumor effect of oncolytic adenovirus against ovarian cancer
Author(s) -
Huang Yao,
Lv Saiqun,
Liu Pinyi,
Ye Zhenlong,
Yang Huan,
Li Linfang,
Zhu Haili,
Wang Ying,
Cui Lianzhen,
Jiang Duqing,
Hao Fangyuan,
Xu Huimin,
Jin Huajun,
Qian Qijun
Publication year - 2020
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12628
Subject(s) - oncolytic virus , oncolytic adenovirus , ovarian cancer , cancer research , fusion protein , cd47 , cancer cell , biology , immunotherapy , cancer , fusion gene , in vivo , antibody , immunology , gene , recombinant dna , tumor cells , biochemistry , genetics , microbiology and biotechnology
Oncolytic viruses armed with therapeutic transgenes of interest show great potential in cancer immunotherapy. Here, a novel oncolytic adenovirus carrying a signal regulatory protein‐α (SIRPα)‐IgG1 Fc fusion gene (termed SG635‐SF) was constructed, which could block the CD47 ‘don't eat me’ signal of cancer cells. A strong promoter sequence (CCAU) was chosen to control the expression of the SF fusion protein, and a 5/35 chimeric fiber was utilized to enhance the efficiency of infection. As a result, SG635‐SF was found to specifically proliferate in hTERT‐positive cancer cells and largely increased the abundance of the SF gene. The SF fusion protein was effectively detected, and CD47 was successfully blocked in SK‐OV3 and HO8910 ovarian cancer cells expressing high levels of CD47. Although the ability to induce cell cycle arrest and cell death was comparable to that of the control empty SG635 oncolytic adenovirus in vitro , the antitumor effect of SG635‐SF was significantly superior to that of SG635 in vivo . Furthermore, CD47 was largely blocked and macrophage infiltration distinctly increased in xenograft tissues of SK‐OV3 cells but not in those of CD47‐negative HepG2 cells, indicating that the enhanced antitumor effect of SG635‐SF was CD47‐dependent. Collectively, these findings highlight a potent antitumor effect of SG635‐SF in the treatment of CD47‐positive cancers.