Improving Retroviral Vectors for Gene Therapy of Breast Cancer
Abstract
This project aims to increase the transduction efficiency and target cell-specificity of retroviral vectors, thereby improving gene transfer to breast cancer cells. We have developed a novel replication-competent retroviral vector system for gene transfer to solid tumors which is highly efficient, as each tumor cell which is successfully transduced becomes itself a virus-producing cell and initiates further infection events even after the initial injection. Through this project, we have tested a number of strategies for targeting these replicating vectors specifically and exclusively to tumor cells, including (1) engineering a single-chain antibody directed against HER-2 into the viral envelope sequence, and (2) insertion of an immunoglobulin-binding domain into the envelope to allow modular conjugation of monoclonal antibodies. While we have successfully achieved incorporation of these modified envelopes into RCR virions and obtained some functional targeting in artificial target cells, we encountered technical difficulties in application of these strategies for targeting true human breast cancer cells. However, we have found that even untargeted RCR vectors exhibit highly tumor selective replication in breast cancer xenograft models in vivo, and the efficient intratumoral transmission of suicide genes via replicative spread of the RCR vector results in significant inhibition of tumor growth upon pro-drug administration.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA419481
Entities
People
- Noriyuki Kasahara
Organizations
- University of Southern California