Regression of AK7 malignant mesothelioma established in immunocompetent mice following intratumoral gene transfer of interferon gamma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-06

AUTHORS

Laurence Cordier Kellerman, Laurence Valeyrie, Nadine Fernandez, Paule Opolon, Jean-Christophe Sabourin, Eve Maubec, Pierre Le Roy, Agnes Kane, Agnes Legrand, Mohamed Amine Abina, Vincent Descamps, Hédi Haddada

ABSTRACT

Malignant mesothelioma (MM) is a lethal tumor linked with a prior exposure to asbestos in which limited progress has been made so far using conventional therapies. MM is an example of a "nonimmunogenic" tumor characterized by a fibrous stroma and an absence of infiltrating T lymphocytes. High levels of transforming growth factor-beta (TGF-beta) produced by mesothelioma cells have been related to the immune tolerance towards the tumor. In order to evaluate the effect of local delivery of cytokines such as interferon gamma (IFN-gamma) by gene transfer, we characterized and used a murine model, AK7, which appeared very similar to human mesothelioma. AK7 cells expressed low levels of major histocompatibility class I and class II antigens and secreted high levels of latent TGF-beta. The TGF-beta pathway in AK7 cells is operative but inefficient because endogenous TGF-beta is predominantly inactive. Treatment of pre-established AK7 tumors by direct intratumoral injection of an adenovirus vector expressing murine IFN-gamma, Ad.mIFN-gamma, led to significant tumor regression. Peripheral tumor infiltration by CD4+ and CD8+ T lymphocytes in the treated tumors appeared to be because of the induction of an immune response. Tumor relapse was observed, which could be due to local TGF-beta secretion by remaining tumor cells. More... »

PAGES

7700594

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.cgt.7700594

DOI

http://dx.doi.org/10.1038/sj.cgt.7700594

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1027629076

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12768194


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