Adenovirus-mediated interferon-beta gene therapy inhibits tumor growth and inhibits metastatic lung tumors in mice
R. Wiewrodt, M. Odaka, P. DeLong, T. Tanaka, V. Kapoor, K. Amin, L. R. Kaiser, S. M. Albelda (Philadelphia, United States Of America; Mainz, Germany)
Source: Annual Congress 2002 - Thoracic oncology: clinical management
Session: Thoracic oncology: clinical management
Session type: Poster Discussion
Number: 1186
Disease area: Respiratory infections, Thoracic oncology
Abstract For non-resectable patients, treatment of lung cancer (LC) is ineffective. In other tumors, immune-modulatory therapies using various interferons (IFN) have shown some promise. We thus evaluated the use of a replication-deficient adenoviral (Ad) vector encoding for the murine IFN-β gene (Ad.muIFN-β) in mouse LC models. L1C2 (a mouse LC cell line syngeneic in immune competent BALB/c) was injected via four routes: intrapleural (i.pl.), intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.). Established tumors were treated with a single dose (1e9 pfu) of Ad.muIFN-β, a control Ad vector (Ad.HSVtk), or saline given via various routes. 80% of animals with intraperitoneal tumors were cured after a single i.p. dose of Ad.IFN-b. A single i.t. dose of Ad.muIFN-β significantly prolonged the survival of BALB/c mice after i.t. tumor (90% survival at 90 days), compared with a median survival for mice treated with i.t. saline (26 days) or AdRSVtk (47 days). In the more aggressive i.pl. model, Ad.muIFN-β doubled median survival and resulted in a at least 25% long term survival, whereas controls were all dead by day 24. Intraperitoneal treatment of animals injected with tumors both i.p. and i.v. led to marked inhibition of the metastatic lung tumors. Rechallanging experiments revealed a protective immunity. Local (intratracheal, intrapleural, and intraperitoneal) delivery of the murine interferon-b gene via an adenoviral vector provided effective local and distant treatment for lung cancers established at various sites, as well as protective acquired immunity.
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R. Wiewrodt, M. Odaka, P. DeLong, T. Tanaka, V. Kapoor, K. Amin, L. R. Kaiser, S. M. Albelda (Philadelphia, United States Of America; Mainz, Germany). Adenovirus-mediated interferon-beta gene therapy inhibits tumor growth and inhibits metastatic lung tumors in mice. Eur Respir J 2002; 20: Suppl. 38, 1186
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