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Intratumoral administration of an adenovirus expressing a kinase dead form of ErbB-2 inhibits tumor growth

Gene Therapy volume 9, pages 898–905 (2002)Cite this article

Abstract

ErbB-2 is amplified or overexpressed in a number of different cancers including breast, ovarian, lung, prostate and stomach. This overexpression leads to enhanced receptor dimer formation and stabilization allowing the receptor to remain in an active state. The clinical consequences of ErbB-2 overexpression include increased tumor aggressiveness, poor prognosis, decreased patient survival and resistance to chemotherapy. As a result, a variety of different strategies are being examined to inhibit its function or expression. In this study, we explored the efficacy of a type 5 recombinant adenovirus encoding a kinase dead form of ErbB-2, AderbB-2Δtk, as a potential therapeutic agent for breast cancer using a murine breast model expressing constitutively active ErbB-2. Co-expression in tumor cells of the kinase dead form of ErbB-2 inhibits receptor activity and induces the death of cells expressing constitutively active ErbB-2. In addition, AderbB-2Δtk exhibits antitumor activity in both immune-competent and immune-deficient animals with increased antitumor activity in the immune-competent animals. The results suggest both immune and non-immune mechanisms contribute to the antitumor efficacy of this vector.

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Acknowledgements

The authors acknowledge the excellent technical help of Duncan Chong, Xueya Feng and Mary Jo Smith. This work was supported by the Canadian Institutes of Health Research, the Breast Cancer Society of Canada, and CANVAC to YW and by the Canadian Breast Cancer Research Initiative to WJM. N Sharan is a recipient of a US Army studentship. WJ Muller is a recipient of CIHR Scientist award.

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Authors and Affiliations

  1. Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada

    K Palmer, N Sharan, P Emtage, J Gauldie, WJ Muller & Y Wan

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Palmer, K., Sharan, N., Emtage, P. et al. Intratumoral administration of an adenovirus expressing a kinase dead form of ErbB-2 inhibits tumor growth. Gene Ther 9, 898–905 (2002). https://doi.org/10.1038/sj.gt.3301712

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