Successful adenovirus-mediated gene transfer in an in vivo model of human malignant mesothelioma.
Malignant mesothelioma remains a frustrating clinical problem with uniformly poor responses to current therapeutic regimens. However, the localized nature of the disease, the potential accessibility of the tumor, and the relative lack of distant metastases make it a particularly attractive candidate for somatic gene therapy. The purpose of this study was to evaluate the ability of an adenoviral vector system to transfer genetic material to human mesothelioma cells in vitro and in vivo. Using a replication-deficient recombinant adenovirus carrying the Escherichia coli lacZ marker gene, we found that human mesothelioma cell lines were susceptible to adenovirus infection. Furthermore, surprisingly effective gene transfer was accomplished within tumor implants of human mesothelioma growing within the peritoneal cavity of immunodeficient mice after intraperitoneal administration of virus. These studies demonstrate that adenoviral vectors hold promise as vehicles to deliver gene therapy in human malignant mesothelioma.
Smythe
W R
WR
Department of Surgery, University of Pennsylvania Medical Center, Philadelphia.
Kaiser
L R
LR
Hwang
H C
HC
Amin
K M
KM
Pilewski
J M
JM
Eck
S J
SJ
Wilson
J M
JM
Albelda
S M
SM
D000005:Abdomen / Q000473:pathology; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D004848:Epithelium / Q000473:pathology; D004926:Escherichia coli / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010997:Pleural Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D011401:Promoter Regions, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics
D005819:Genetic Markers; D001616:beta-Galactosidase