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  • Viral Transfer Technology
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Recombinant adenoviral vectors have adjuvant activity and stimulate T cell responses against tumor cells

Gene Therapy volume 7, pages 1410–1416 (2000)Cite this article

Abstract

The host-immune response against adenoviruses forms a major obstacle for their use as gene therapy vectors for treatment of genetic defects. None the less, they are the preferred vectors for in vivo gene transfer in experimental gene therapy protocols for cancer. In this article we demonstrate the antitumor efficacy of adenovirus-mediated transfer of human interleukin-2 cDNA in the rat-CC531 model for hepatic metastases of colorectal cancer: intratumoral administration of 108 plaque-forming units of the hIL-2-expressing adenoviral vector, AdCAIL-2, resulted in a cessation of tumor growth in 80% of the injected tumors. In control groups receiving AdCnull, a vector with the same viral backbone, but lacking transgene expression, none of the tumors responded. However, intratumoral treatment with this vector significantly enhanced tumor regression induced by systemic IL-2 protein treatment, which was used as a positive control. In addition we show, by performing delayed-type of hypersensitivity assays, that AdCnull when injected intratumorally enhances recognition of tumor antigens by T lymphocytes to the same extent as intratumoral treatment with the IL-2-expressing vector. The replication-deficient adenoviruses appear to have a therapeutic advantage in cytokine-mediated immunotherapy: even adenovirus vectors that do not express a transgene, show adjuvant activity and stimulate an antitumor immune response.

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Acknowledgements

We would like to thank Dr F Graham for kindly providing the AdCAIL-2 adenoviral vector, M Rabelink for expert technical assistance, and Drs R Offringa, M Hagenaars, JM van Noort, JJ Bajramovič, and H van Ormondt for helpful discussions and critically reading this manuscript.

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Author notes

  1. S B Geutskens and M M van der Eb: Both authors contributed equally to this work and should both be regarded as ‘first author’

Authors and Affiliations

  1. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

    S B Geutskens, M M van der Eb, S J Cramer & R C Hoeben

  2. Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

    M M van der Eb, L E Jonges, N G Ensink & P J K Kuppen

  3. Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands

    A C Plomp

Authors
  1. S B Geutskens
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  2. M M van der Eb
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  4. L E Jonges
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Geutskens, S., van der Eb, M., Plomp, A. et al. Recombinant adenoviral vectors have adjuvant activity and stimulate T cell responses against tumor cells. Gene Ther 7, 1410–1416 (2000). https://doi.org/10.1038/sj.gt.3301251

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