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Immunocompetent, Semi-Permissive Cotton Rat Tumor Model for the Evaluation of Oncolytic Adenoviruses

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Part of the book series: Methods in Molecular Medicine ((MIMM,volume 130))

Abstract

Oncolytic adenovirus (Ad) vectors belong to a new class of cancer therapy agents that destroy cancer cells as part of the virus’s lytic infectious cycle. In this chapter we describe an immunocompetent, semi-permissive cotton rat tumor model to evaluate the safety and efficacy of oncolytic Ad vectors. With this model one can investigate the effect of the host immune system on the vector-tumor interaction as well as the vector’s effect on normal host cells in vivo. This chapter describes procedures for analyzing the growth and cytolytic properties of oncolytic Ad vectors in cotton rat cells in vitro. We discuss handling and husbandry issues and techniques for subcutaneous, intratumoral, and intravenous injection of cotton rats. We present methods for generating subcutaneous tumors in cotton rats and assessing the efficacy of Ad vectors upon intratumoral injection. Also, we discuss procedures for determining the biodistribution of a replicating Ad in cotton rats.

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References

  1. Berencsi, K., Uri, A., Valyi-Nagy, T., et al. (1994) Early region 3-replacement adenovirus recombinants are less pathogenic in cotton rats and mice than early region 3-deleted viruses. Lab. Invest. 7, 350–358.

    Google Scholar 

  2. Ginsberg, H. S., Lundholm-Beauchamp, U., Horswood, R.L., et al. (1989) Role of early region 3 (E3) in pathogenesis of adenovirus disease. Proc. Natl. Acad. Sci. USA 86, 3823–3827.

    Article  PubMed  CAS  Google Scholar 

  3. Pacini, D. L., Dubovi, E. J., and Clyde, W. A., Jr. (1984) A new animal model for human respiratory tract disease due to adenovirus. J. Infect. Dis. 150, 92–97.

    PubMed  CAS  Google Scholar 

  4. Prince, G. A., Porter, D. A., Jenson, A. B., Horswold, R. L., Chanock, R. M., and Ginsberg, H. S. (1993) Pathogenesis of adenovirus type 5 pneumonia in cotton rats (sigmodon hispidus). J. Virol. 67, 101–111.

    PubMed  CAS  Google Scholar 

  5. Tsai, J. C., Garlinghouse, G., McDonnell, P. J., and Trousdale, M. D. (1992) An experimental animal model of adenovirus-induced ocular disease. The cotton rat. Arch. Ophthalmol. 110, 1167–1170.

    PubMed  CAS  Google Scholar 

  6. Toth, K., Spencer, J.F., Tollefson, A. E., et al. (2005) Cotton rat tumor model for the evaluation of oncolytic adenoviruses. Hum. Gene Ther. 16, 139–146.

    Article  PubMed  CAS  Google Scholar 

  7. Doronin, K., Toth, K., Kuppuswamy, M., Ward, P., Tollefson, A. E., and Wold, W. S. M. (2000) Tumor-specific, replication-competent adenovirus vectors overexpressing the Adenovirus Death Protein. J. Virol. 74, 6147–6155.

    Article  PubMed  CAS  Google Scholar 

  8. Doronin, K., Kuppuswamy, M., Toth, K., et al. (2001) Tissue-specific, tumor-selective, replication-competent adenovirus vector for cancer gene therapy. J. Virol. 75, 3314–3324.

    Article  PubMed  CAS  Google Scholar 

  9. Doronin, K., Toth, K., Kuppuswamy, M., Krajcsi, P., Tollefson, A.E., and Wold, W. S.M. (2003) Overexpression of the ADP (E3-11.6K) protein increases cell lysis and spread of adenovirus. Virology 305, 378–387.

    Article  PubMed  CAS  Google Scholar 

  10. Toth, K., Djeha, H., Ying, B. L., et al. (2004) An oncolytic adenovirus vector combining enhanced cell-to-cell spreading, mediated by the ADP cytolytic protein, with selective-replication in cancer cells with deregulated Wnt signaling. Cancer Res. 64, 3638–3644.

    Article  PubMed  CAS  Google Scholar 

  11. Faith, R. E., Montgomery, C. A., Durfee, W. J., Aguilar-Cordova, E., and Wyde, P. R. (997) The cotton rat in biomedical research. Lab. Anim. Sci. 47, 337–345.

    PubMed  CAS  Google Scholar 

  12. Ward, L. E. (2001) Handling the cotton rat for research. Lab Animal 30, 45–50.

    PubMed  CAS  Google Scholar 

  13. Toth, K., Tarakanova, V., Doronin, K., et al. (2003) Radiation increases the activity of oncolytic adenovirus cancer gene therapy vectors that overexpress the ADP (E3-11.6K) protein. Cancer Gene Ther. 10, 193–200.

    Article  PubMed  CAS  Google Scholar 

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© 2007 Humana Press Inc.

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Toth, K., Spencer, J.F., Wold, W.S.M. (2007). Immunocompetent, Semi-Permissive Cotton Rat Tumor Model for the Evaluation of Oncolytic Adenoviruses. In: Wold, W.S.M., Tollefson, A.E. (eds) Adenovirus Methods and Protocols. Methods in Molecular Medicine, vol 130. Humana Press. https://doi.org/10.1385/1-59745-166-5:157

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  • DOI: https://doi.org/10.1385/1-59745-166-5:157

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-598-9

  • Online ISBN: 978-1-59745-166-6

  • eBook Packages: Springer Protocols

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