Am. J. Respir. Cell Mol. Biol., Vol 13, No. 1, 07 1995, 7-16.
Gene therapy using adenovirus carrying the herpes simplex-thymidine kinase gene to treat in vivo models of human malignant mesothelioma and lung cancer
HC Hwang, WR Smythe, AA Elshami, JC Kucharczuk, KM Amin, JP Williams, LA Litzky, LR Kaiser and SM Albelda
Department of Medicine; University of Pennsylvania Medical Center, Philadelphia, USA.
Previous studies have shown adenoviral transfer of the herpes simplex virus
thymidine kinase (HSVtk) gene followed by the anti-viral drug ganciclovir
(GCV) can be used to successfully treat established human mesothelioma
tumors growing within the peritoneal cavities of severe combined immune
deficient (SCID) mice. These findings raised a number of questions
important to the applicability, efficiency, and safety of this treatment
strategy. In this report, we have further characterized the use of
recombinant adenovirus carrying the HSVtk gene to treat mesothelioma and
other localized malignancies. Our results indicate that the Ad.RSVtk/GCV
system is effective in causing tumor regression in animals inoculated with
another mesothelioma cell line and a lung cancer cell line and that animals
with bulky disease can be successfully treated. Effects are seen at a wide
range of virus doses and significant anti-tumor activity is present at
doses of ganciclovir that are clinically achievable. Finally, this
treatment approach appears safe, with limited dissemination of virus using
a sensitive RT- PCR detection system. These studies further characterize
the use of adenoviral transfer of the HSVtk gene to treat experimental
mesothelioma and suggest that clinical trials using this approach may be
feasible.
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Copyright © 1995 American Thoracic Society.
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