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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This work is supported by the Health & Medical Technology R&D program of Korea (A060195).
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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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DOI: https://doi.org/10.1038/cgt.2009.78
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