Format

Send to

Choose Destination
J Clin Invest. 2000 Sep;106(6):763-71.

Selectivity of a replication-competent adenovirus for human breast carcinoma cells expressing the MUC1 antigen.

Author information

1
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

The DF3/MUC1 gene is aberrantly overexpressed in human breast and other carcinomas. Previous studies have demonstrated that the DF3/MUC1 promoter/enhancer confers selective expression of diverse transgenes in MUC1-positive breast cancer cells. In this study, we show that an adenoviral vector (Ad.DF3-E1) in which the DF3/MUC1 promoter drives expression of E1A selectively replicates in MUC1-positive breast cancer cells. We also show that Ad.DF3-E1 infection of human breast tumor xenografts in nude mice is associated with inhibition of tumor growth. In contrast to a replication-incompetent adenoviral vector that infects along the injection track, Ad.DF3-E1 infection was detectable throughout the tumor xenografts. To generate an Ad.DF3-E1 vector with the capacity for incorporating therapeutic products, we inserted the cytomegalovirus (CMV) promoter upstream of the TNF cDNA. Infection with Ad.DF3-E1/CMV-TNF was associated with selective replication and production of TNF in cells that express MUC1. Moreover, treatment of MUC1-positive, but not MUC1-negative, xenografts with a single injection of Ad.DF3-E1/CMV-TNF was effective in inducing stable tumor regression. These findings demonstrate that the DF3/MUC1 promoter confers competence for selective replication of Ad.DF3-E1 in MUC1-positive breast tumor cells, and that the antitumor activity of this vector is potentiated by integration of the TNF cDNA.

PMID:
10995787
PMCID:
PMC381391
DOI:
10.1172/JCI9180
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center