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

Hortobagyi GN, Ueno NT, Xia W, Zhang S, Wolf JK, Putnam JB, Weiden PL, Willey JS, Carey M, Branham DL, Payne JY, Tucker SD, Bartholomeusz C, Kilbourn RG, De Jager RL, Sneige N, Katz RL, Anklesaria P, Ibrahim NK, Murray JL, Theriault RL, Valero V, Gershenson DM, Bevers MW, Huang L, Lopez-Berestein G, Hung MC
J Clin Oncol. 2001 19 (14): 3422-33

PMID: 11454891 · DOI:10.1200/JCO.2001.19.14.3422

PURPOSE - Preclinical studies have demonstrated that the adenovirus type 5 E1A gene is associated with antitumor activities by transcriptional repression of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of E1A gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a phase I clinical trial.

PATIENTS AND METHODS - An E1A gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patients with advanced cancer of the breast (n = 6) or ovary (n = 12).

RESULTS - E1A gene expression in tumor cells was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression was accompanied by HER-2/neu downregulation, increased apoptosis, and reduced proliferation. The most common treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at the injection sites.

CONCLUSION - These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the E1A gene.

MeSH Terms (24)

Adenovirus E1A Proteins Adult Aged Apoptosis Breast Neoplasms Cholesterol Cytokines Female Gene Expression Genes, erbB-2 Genetic Therapy Gene Transfer, Horizontal Humans Immunohistochemistry Injections In Situ Nick-End Labeling Ki-67 Antigen Liposomes Middle Aged Ovarian Neoplasms Peritoneal Cavity Reverse Transcriptase Polymerase Chain Reaction Thorax Tumor Cells, Cultured

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