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Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus

Cancer Gene Therapy volume 11, pages 532–538 (2004)Cite this article

Abstract

Although gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers, few studies have explored this possibility for uterine cervical cancer. MN/CA9 is a transmembrane glycoprotein that was first identified in the human cervical carcinoma cell line, HeLa. Since MN/CA9 protein is highly expressed in uterine cervical cancer tissues, but not in normal cervix, we constructed a tumor-specific replication-competent adenoviral vector utilizing MN/CA9 promoter (Ad-MN/CA9-E1a), which can replicate only in MN/CA9-expressing cells. Infection of Ad-MN/CA9-E1a to MN/CA9-positive uterine cervical cancer cells (HeLa, C-33 A and SiHa) resulted in much stronger Ad5 E1a protein expressions compared with MN/CA9-negative cells (SK-RC-29), suggesting a tissue-specific replication of this recombinant adenovirus. In vitro cytotoxicity assay revealed that the growth of MN/CA9-positive cells was significantly inhibited with 0.01–1 MOI of Ad-MN/CA9-E1a, but the growth of MN/CA9-negative cells (SK-RC-29) could only be inhibited by as many as 100 MOI. Intratumoral injection of Ad-MN/CA9-E1a effectively induced growth delay of HeLa tumors in nude mice. These results suggest that a novel replication-competent adenoviral vector mediated by MN/CA9 promoter, Ad-MN/CA9-E1a, can selectively replicate in MN/CA9-expressing tumors with cytotoxic effects and may be utilized for the treatment of uterine cervical cancer.

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Acknowledgements

We thank Dr Hee Jae Joo, Department of Pathology, for assistance in the preparation and interpretation of histologic studies. This work was supported by 2001 grant from the Department of Medical Sciences, The Graduate School, Ajou University.

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Authors and Affiliations

  1. Department of Medical Oncology, Ajou University School of Medicine, Suwon, Korea

    Ho Yeong Lim

  2. Department of Urology, Ajou University School of Medicine, Suwon, Korea

    Miwon Ahn & Se Joong Kim

  3. Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, Korea

    Hyun Cheol Chung

  4. Department of Urology, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Thomas A Gardner, Chinghai Kao & Sang-Jin Lee

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  1. Ho Yeong Lim
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Correspondence to Se Joong Kim.

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Lim, H., Ahn, M., Chung, H. et al. Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus. Cancer Gene Ther 11, 532–538 (2004). https://doi.org/10.1038/sj.cgt.7700732

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