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High-dose chemotherapy augments the efficacy of recombinant adenovirus vaccines and improves the therapeutic outcome

Cancer Gene Therapy volume 16, pages 338–350 (2009)Cite this article

Abstract

We have investigated the therapeutic potential of a prototypic melanoma vaccine based on recombinant adenovirus expressing human dopachrome tautomerase in the B16F10 murine melanoma model. We found that in the presence of a tumor, the magnitude of T-cell immunity evoked by the vaccine was significantly reduced. This impairment was compounded by defects in cytokine production and degranulation within the tumor-infiltrating lymphocytes (TILs). We showed that the combination of vaccination with high-dose cyclophosphamide was able to skew the response toward the target antigen and enhanced both the quantity and quality of antigen-specific CD8+ and CD4+ T-cell responses in tumor-bearing mice, which resulted in the inhibition of tumor growth. Furthermore, when tumor-specific antigens were targeted by the vaccine, the combination therapy could actually produce tumor regression, which appeared to result from the high frequency of antigen-specific T cells. These data show that recombinant adenovirus vaccines are compatible with conventional high-dose chemotherapy and that the combined treatment results in improved therapeutic outcomes relative to either agent individually.

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Acknowledgements

We thank Carole Evelegh for preparing the viruses used in these experiments. This study was supported by the Ontario Cancer Research Network. YW is a CIHR New Investigator. FB was supported by the Swiss National Science Foundation and the Swiss Cancer League. NG was supported by a research studentship from the National Cancer Institute of Canada.

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Authors and Affiliations

  1. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada

    N Grinshtein, M Ventresca, R Margl, D Bernard, T-C Yang, J B Millar, J Hummel, Y Wan & J L Bramson

  2. ISREC (Swiss Institute for Experimental Cancer Research), School of Life Sciences, Ecole Polytechnique Féderale de Lausanne (EPFL), Epalinges, Switzerland

    F Beermann

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Correspondence to J L Bramson.

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Grinshtein, N., Ventresca, M., Margl, R. et al. High-dose chemotherapy augments the efficacy of recombinant adenovirus vaccines and improves the therapeutic outcome. Cancer Gene Ther 16, 338–350 (2009). https://doi.org/10.1038/cgt.2008.89

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