A Novel Strategy for Targeting Therapeutic Retroviral Vectors Specifically to Prostate Cancer Cells.
Abstract
We are developing a system that will be useful for targeting therapeutic retroviral vectors specifically to prostate cancer cells using novel retroviral receptor-ligand bridge proteins that bind to specific cell surface ligand receptors. Using bridge proteins comprised of the TVA or TVB receptors (for subgroups A or B avian leukosis viruses (ALV), respectively), fused to human epidermal growth factor (EGF), viral targeting was achieved by preloading the bridge proteins onto cell surface EGF receptors or virions. In addition, we have demonstrated increased levels of viral vector targeting by incorporating selected amino acid substitutions into TVA-EGF. We have also generated a bridge protein comprised of TVA fused to neuregulin (NRG) which binds specifically to cell surface NRG receptors. These receptors are often up-regulated on prostate cancer cells and thus represent an attractive target for this method of therapeutic gene delivery. We have also shown that it is possible to target retroviral infection through the use of a bridge protein comprised of TVA fused to a single chain antibody specific for a mutant form of the EGF receptor that is found exclusively on cancer cell types. Thus, this appears to be a highly versatile and general viral targeting approach.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA378070
Entities
People
- John Young
Organizations
- Harvard University