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Conditionally replicating E1B-deleted adenovirus driven by the squamous cell carcinoma antigen 2 promoter for uterine cervical cancer therapy

Cancer Gene Therapy volume 15, pages 526–534 (2008)Cite this article

Abstract

Cervical cancer is the second most common type of malignant tumor among women worldwide. When the disease is confined locally, it can be controlled with surgical resection and radiotherapy. However, patients with recurrent or metastatic disease often have a poor prognosis. Measurement of serum levels of squamous cell carcinoma (SCC) antigens has been widely used as serological markers for SCC of uterine cervix. Recently, it has been demonstrated that cervical cancer patients with elevated squamous cell carcinoma antigen-2 (SCCA2) expression in tumor cells carry a poor prognosis. Here, by using a luciferase reporter assay, we show that SCCA2 promoter was active in SCCA2-producing human cervical cancer cell lines, including Cx, Cxwj, SiHa and HeLa cells, but relatively quiescent in normal cervical epithelial cells. We then developed a conditionally replicating adenovirus, designated Ad-KFH, under the transcriptional control of the SCCA2 promoter. This E1B-55 kDa-deleted oncolytic adenovirus replicated specifically in and lysed SCCA2-producing cervical cancer cells. Furthermore, in a peritoneal metastatic tumor model, Ad-KFH retarded Cxwj tumor growth in NOD/severe combined immunodeficient mice and prolonged survival of tumor-bearing mice, especially when combined with cisplatin. These results suggest that Ad-KFH may provide a new strategy of gene therapy for advanced or recurrent uterine cervical cancer.

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Acknowledgements

We are indebted to Dr TC Wu (Department of Pathology, Johns Hopkins University, USA) for providing retroviral vector LXSN expressing HPV type 16 E6 and E7. This work was supported by grants from the National Science Council (NSC 93-2314-B-006-074 and NSC 94-2314-B-384-010) and Center of Excellence for Clinical Trial and Research in Oncology Specialty, Ministry of Health, Taiwan.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan, Taiwan

    K-F Hsu, M-R Shen, W-J Chung & C-Y Chou

  2. Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan, Taiwan

    K-F Hsu, C-L Wu & A-L Shiau

  3. Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan

    C-L Wu

  4. Department of Obstetrics and Gynecology, Chi Mei Foundation Hospital, Tainan, Taiwan

    S-C Huang

  5. Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan

    J-L Hsieh, Y-S Huang, Y-F Chen & A-L Shiau

  6. Department of Pharmacology, National Cheng Kung University Medical College, Tainan, Taiwan

    M-R Shen

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  1. K-F Hsu
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Correspondence to C-Y Chou or A-L Shiau.

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Hsu, KF., Wu, CL., Huang, SC. et al. Conditionally replicating E1B-deleted adenovirus driven by the squamous cell carcinoma antigen 2 promoter for uterine cervical cancer therapy. Cancer Gene Ther 15, 526–534 (2008). https://doi.org/10.1038/cgt.2008.37

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