S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Genetic immunotherapy of lung cancer using conditionally replicating adenovirus and adenovirus-interferon-beta
- Park, M-Y; Kim, D. R.; Jung, H. W.; Yoon, H-I; Lee, C-T; Lee, J. H.
- Issue Date
- NATURE PUBLISHING GROUP
- CANCER GENE THERAPY; Vol.17 5; 356-364
- conditionally replicating adenovirus; lung cancer; genetic immunotherapy; adenovirus-IFN-beta
- 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-beta (ad-IFN-beta). We investigated the efficacy of this therapy in an immunocompetent mouse tumor model. Transduction with CRAd (Delta 24RGD) induced cytolysis in a mouse lung cancer cell line (Lewis lung carcinoma (LLC)). Combined transduction of ad-IFN-beta and Delta 24RGD in the LLC cells induced a greater and more prolonged production of IFN-beta. Media transfer from the LLC-Delta 24RGD-ad-IFN-beta to untransduced LLC cells induced the production of IFN-beta; these results confirmed the replication and release of ad-IFN-beta. LLC cells transduced with ad-IFN-beta and Delta 24RGD had decreased tumorigenicity in syngeneic mice. Tumor vaccination with irradiated LLC-ad-IFN-beta-Delta 24RGD 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 Delta 24RGD to ad-IFN-beta aided the replication of ad-IFN-beta in the LLC cells. A high local concentration of IFN-beta 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. Cancer Gene Therapy (2010) 17, 356-364; doi:10.1038/cgt.2009.78; published online 6 November 2009
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