Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: A phase I clinical trial

Citation
Gn. Hortobagyi et al., Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: A phase I clinical trial, J CL ONCOL, 19(14), 2001, pp. 3422-3433
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
JOURNAL OF CLINICAL ONCOLOGY
ISSN journal
0732-183X → ACNP
Volume
19
Issue
14
Year of publication
2001
Pages
3422 - 3433
Database
ISI
SICI code
0732-183X(20010715)19:14<3422:CLEGTT>2.0.ZU;2-9
Abstract
Purpose: preclinical studies have demonstrated that the adenovirus type 5 E IA gene is associated with antitumor activities by transcriptional repressi on of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is kno wn to induce regression of HER-2/neu-overexpressing breast and ovarian canc ers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of EIA gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing b reast and ovarian cancers in a phase I clinical trial. Patients and Methods: An EIA gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patie nts with advanced cancer of:the breast (n = 6) or ovary(n = 12). Results: ETA gene expression in tumor cells was detected by immunohistochem ical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression wets accompanied by HER-2/neu down-regulation, increased a poptosis, and reduced proliferation. The most common treatment-related toxi cities were fever, nausea, vomiting, and/or discomfort at the injection sit es. Conclusion: These results argue for the feasibility of intracavitary DCC-E1 A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the EIA gene. (C) 2 001 by American Society of Clinical Oncology.