Treatment of Primary and Metastatic Breast Cancer by an Armed Replicating Adenoviral Vector
Abstract
Oncolytic replication-selective adenoviruses are a new class of anticancer agents with great therapeutic potential. The ability of replication-selective viruses to amplify the initial viral dose has been exploited by engineering oncolytic adenoviruses to deliver therapeutic transgenes. In this Exploration Award, we are testing the concept that an oncolytic adenovirus can be armed with a therapeutic gene that will exert a systemic effect in the treatment of breast cancer. Breast cancer most commonly metastasizes to the skeleton. Thus, a treatment that combines eradication of the primary tumor with inhibition of osteolytic bone metastases would be a highly beneficial addition to the therapeutic armamentarium. We hypothesize that an oncolytic adenovirus armed with the osteoprotegerin (OPG) gene would be able to eradicate a primary breast cancer tumor by oncolysis, and that secretion of OPG from the infected and lysed cells into the systemic circulation would inhibit osteolytic bone metastases of the breast cancer. Thus, we propose a new class of therapeutic agent for the treatment of breast cancer. To date, we have constructed a replication-defective adenoviral vector expressing human OPG fused with the Fc domain of human lgG, and have evaluated the efficacy of the armed replicating adenoviral vector in vitro.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA430586
Entities
People
- Joanne T. Douglas
Organizations
- University of Alabama