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A SIRP?-Fc fusion protein enhances the antitumor effect of oncolytic adenovirus against ovarian cancer.

ABSTRACT: Oncolytic viruses armed with therapeutic transgenes of interest show great potential in cancer immunotherapy. Here, a novel oncolytic adenovirus carrying a signal regulatory protein-? (SIRP?)-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.

SUBMITTER: Huang Y

PROVIDER: S-EPMC7053234 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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A SIRPα-Fc fusion protein enhances the antitumor effect of oncolytic adenovirus against ovarian cancer.

Huang Yao Y Lv Sai-Qun SQ Liu Pin-Yi PY Ye Zhen-Long ZL Yang Huan H Li Lin-Fang LF Zhu Hai-Li HL Wang Ying Y Cui Lian-Zhen LZ Jiang Du-Qing DQ Hao Fang-Yuan FY Xu Hui-Min HM Jin Hua-Jun HJ Qian Qi-Jun QJ

Molecular oncology 20200207 3

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 ...[more]

PMID: 31899582

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Dataset Information

A SIRP?-Fc fusion protein enhances the antitumor effect of oncolytic adenovirus against ovarian cancer.

Publications

A SIRPα-Fc fusion protein enhances the antitumor effect of oncolytic adenovirus against ovarian cancer.

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