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Experimental Therapeutics, Preclinical Pharmacology |
Induces Antiproliferative and Antitumoral Responses in Malignant Mesothelioma1
Equipe INSERM EMI.99.09 [F. G., Y. P., I. M., S. M., J. L. C., M-C. J.] and Unité INSERM U448 [C. B.], Faculté de Médecine Paris XII, 94010 Creteil Cedex, France; Service de Pneumologie, Centre Hospitalier Intercommunal, 94010 Créteil Cedex, France [I. M.]; and UMR INRA-AFSSA 1161, Ecole Nationale Vétérinaire dAlfort, 94704 Maisons-Alfort, France [M. E.]
Purpose: The aim of the work was to investigate the effects of adenovirus(Ad)-mediated IFN
gene transfer on human mesothelioma (HM) cell proliferation in vitro and growth in nude mice.
Experimental Design: We constructed an E1E3-deleted replication-defective recombinant Ad carrying the human IFN
gene (Ad-IFN
) and tested its activity in vitro on HM cell lines established in our laboratory and in a nude mice model.
Results: In vitro, infection of HM cells with Ad-IFN
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
. In nude mice, s.c. inoculation of HM cells from one responsive HM cell line previously infected with Ad-IFN
resulted in a delay in tumor development, and injection of Ad-IFN
in preestablished tumors restrained tumor development.
Conclusions: These results indicate for the first time that HM cells are efficiently transduced by Ad-IFN
and produce an active cytokine for several days. IFN
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.
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