Adenovirus-mediated interferon α gene transfer induces regional direct cytotoxicity and possible systemic immunity against pancreatic cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-08

AUTHORS

M Ohashi, K Yoshida, M Kushida, Y Miura, S Ohnami, Y Ikarashi, Y Kitade, T Yoshida, K Aoki

ABSTRACT

We previously demonstrated a characteristically high sensitivity of pancreatic cancer cells to interferon alpha (IFN-alpha) gene transfer, which induced a more prominent growth suppression and cell death in pancreatic cancer cells than in other types of cancers and normal cells. The IFN-alpha protein can exhibit both direct cytotoxicity and indirect immunological antitumour activity. Here, we dissected and examined the two mechanisms, taking advantage of the fact that IFN-alpha did not show any cross-species activity in its in vivo effect. When a human IFN-alpha adenovirus was injected into subcutaneous xenografts of human pancreatic cancer cells in nude mice, tumour growth was significantly suppressed due to cell death in an adenoviral dose-dependent manner. The IFN-alpha protein concentration was markedly increased in the injected subcutaneous tumour, but leakage of the potent cytokine into the systemic blood circulation was minimal. When a mouse IFN-alpha adenovirus was injected into the same subcutaneous tumour system, all mice showed significant tumour inhibition, an effect that was dependent on the indirect antitumour activities of IFN-alpha, notably a stimulation of natural killer cells. Moreover, in this case, tumour regression was observed not only for the injected subcutaneous tumours but also for the untreated tumours at distant sites. This study suggested that a local IFN-alpha gene therapy is a promising therapeutic strategy for pancreatic cancer, due to its dual mechanisms of antitumour activities and lack of significant toxicity. More... »

PAGES

6602713

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6602713

DOI

http://dx.doi.org/10.1038/sj.bjc.6602713

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002588566

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16106250


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