Ad-IFN gamma induces antiproliferative and antitumoral responses in malignant mesothelioma.

Abstract

The aim of the work was to investigate the effects of adenovirus(Ad)-mediated IFN gamma gene transfer on human mesothelioma (HM) cell proliferation in vitro and growth in nude mice. We constructed an E1E3-deleted replication-defective recombinant Ad carrying the human IFN gamma gene (Ad-IFN gamma) and tested its activity in vitro on HM cell lines established in our laboratory and in a nude mice model. In vitro, infection of HM cells with Ad-IFN gamma led to a prolonged production of an active cytokine in the 10 HM cell lines tested and also led to an antiproliferative effect on the HM cells previously demonstrated as responsive to exogenous recombinant human IFN gamma. In nude mice, s.c. inoculation of HM cells from one responsive HM cell line previously infected with Ad-IFN gamma resulted in a delay in tumor development, and injection of Ad-IFN gamma in preestablished tumors restrained tumor development. These results indicate for the first time that HM cells are efficiently transduced by Ad-IFN gamma and produce an active cytokine for several days. IFN gamma produced by gene transfer is shown to have both an antiproliferative effect in vitro and an antitumoral effect in vivo in a nude mice model.