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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-05

AUTHORS

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

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-beta (ad-IFN-beta). We investigated the efficacy of this therapy in an immunocompetent mouse tumor model. Transduction with CRAd (Delta24RGD) induced cytolysis in a mouse lung cancer cell line (Lewis lung carcinoma (LLC)). Combined transduction of ad-IFN-beta and Delta24RGD in the LLC cells induced a greater and more prolonged production of IFN-beta. Media transfer from the LLC-Delta24RGD-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 Delta24RGD had decreased tumorigenicity in syngeneic mice. Tumor vaccination with irradiated LLC-ad-IFN-beta-Delta24RGD 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 Delta24RGD 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. More... »

PAGES

356

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cgt.2009.78

DOI

http://dx.doi.org/10.1038/cgt.2009.78

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050393716

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19893592


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