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Genetic immunotherapy of lung cancer using conditionally replicating adenovirus and adenovirus-interferon-β

Cancer Gene Therapy volume 17, pages 356–364 (2010)Cite this article

Abstract

Genetic immunotherapy is considered an ideal treatment modality for cancer because of its systemic nature. This study was designed to develop a potent novel genetic immunotherapy by combining conditionally replicating adenovirus (CRAd) and replication-defective adenovirus expressing interferon-β (ad-IFN-β). We investigated the efficacy of this therapy in an immunocompetent mouse tumor model. Transduction with CRAd (Δ24RGD) induced cytolysis in a mouse lung cancer cell line (Lewis lung carcinoma (LLC)). Combined transduction of ad-IFN-β and Δ24RGD in the LLC cells induced a greater and more prolonged production of IFN-β. Media transfer from the LLC-Δ24RGD-ad-IFN-β to untransduced LLC cells induced the production of IFN-β; these results confirmed the replication and release of ad-IFN-β. LLC cells transduced with ad-IFN-β and Δ24RGD had decreased tumorigenicity in syngeneic mice. Tumor vaccination with irradiated LLC-ad-IFN-β-Δ24RGD showed a significant increase in the survival of tumor-bearing syngeneic mice compared with mice with a single transduced LLC vaccination; this was mediated by an enhanced cytotoxic T-lymphocyte response against the LLC cells. The results of this study showed that cotransduced Δ24RGD to ad-IFN-β aided the replication of ad-IFN-β in the LLC cells. A high local concentration of IFN-β and local release of tumor antigen by CRAd induced strong antitumor immunity. This combination strategy might provide a powerful means by which ad-cytokines and CRAd can be combined and other adenoviruses expressing different cytokines might also be used.

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Acknowledgements

This work is supported by the Health & Medical Technology R&D program of Korea (A060195).

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Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-Do, Republic of Korea

    M-Y Park, D R Kim, H W Jung, H-I Yoon, J H Lee & C-T Lee

  2. Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Lung Institute, Seoul National University College of Medicine, Gyeonggi-Do, Republic of Korea

    H-I Yoon, J H Lee & C-T Lee

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  1. M-Y Park
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Correspondence to C-T Lee.

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Park, MY., Kim, D., Jung, H. et al. Genetic immunotherapy of lung cancer using conditionally replicating adenovirus and adenovirus-interferon-β. Cancer Gene Ther 17, 356–364 (2010). https://doi.org/10.1038/cgt.2009.78

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