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Intratumoral coinjection of two adenoviral vectors expressing functional interleukin-18 and inducible protein-10, respectively, synergizes to facilitate regression of established tumors

Cancer Gene Therapy volume 9, pages 533–542 (2002)Cite this article

Abstract

We have constructed two recombinant adenoviral vectors AdVIP-10 and AdVIL-18 expressing the functional chemokine IFN-γ inducible protein (IP)-10 and cytokine interleukin (IL)-18, respectively. Injection of either AdVIP-10 or AdVIL-18 subcutaneously into tumor nodules derived from the J558 murine myeloma cell line delayed some tumor growth but it was not curative in all cases. Coinjection of these two vectors at the same tumor nodule not only significantly suppressed the tumor growth, but also cured established tumors in 8 of 10 (80% tumor free) mice. The latter treatment stimulated T-cell infiltration into tumors in association with tumor necrosis formation, induced a type 1 immune response and induced the activation of J558 tumor–specific cytotoxic T lymphocytes. Moreover, the antitumor activity of IP-10 and IL-18 combined gene therapy was significantly diminished in mice with depletion of either CD4+ (50% tumor free) or CD8+ (40% tumor free) T cells, and completely lost (0% tumor free) in T cell–deficient nude and IFN-γ knockout mice, indicating the critical roles of T cells and IFN-γ in this therapeutical model. Taken together, the findings of this study demonstrate that the combined use of two adenoviral vectors expressing IP-10 and IL-18, respectively, synergize to facilitate regression of established tumors. These observations also suggest the potential use of double-recombinant adenoviral vectors expressing chemokines and immunomodulatory cytokines in cancer gene therapy.

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Acknowledgements

This study was supported by a research grant (ROP-15151) from the Canadian Institute of Health Research. We thank Dr H Tabel for his useful comments on this manuscript and Mr X Bi for his technical support in this study.

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Authors and Affiliations

  1. Research Unit, Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon, S7N 4H4, Saskatchewan, Canada

    Yongqing Liu, Hui Huang & Jim Xiang

  2. Department of Oncology, University of Saskatchewan, Saskatoon, S7N 0W0, Saskatchewan, Canada

    Yongqing Liu, Hui Huang & Jim Xiang

  3. Department of Pathology, University of Saskatchewan, Saskatoon, S7N 0W0, Saskatchewan, Canada

    Anurag Saxena

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  1. Yongqing Liu
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  2. Hui Huang
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  4. Jim Xiang
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Correspondence to Jim Xiang.

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Liu, Y., Huang, H., Saxena, A. et al. Intratumoral coinjection of two adenoviral vectors expressing functional interleukin-18 and inducible protein-10, respectively, synergizes to facilitate regression of established tumors. Cancer Gene Ther 9, 533–542 (2002). https://doi.org/10.1038/sj.cgt.7700466

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