Development of Gutless Adenoviral Vectors Encoding Anti Angiogenic Proteins for Therapy of Prostate Cancer
Abstract
The current work describes the development of technologies for long-term viral expression of soluble VEGF receptor anti-angiogenic proteins for therapeutic use in prostate cancer. Two technologies are described, "Gutless" adenoviruses and Adeno-associated viruses (AAV). Gutless adenoviruses have been reported to be capable of > 1 year trans gene expression but their large-scale production is severely limited by helper virus and replication-competent adenovirus contamination. Several approaches for generation for pure gutless adenoviruses expressing the anti-angiogenic soluble Flk-l VEGF receptor, towards achieving therapeutic responses which are more durable than conventional adenoviruses: (1) generation of a gutless adenoviral production method using 1-Scel-dependent packaging signal deleting and viral genome recombination to inactivate helper virus, (2) generation of completion cell lines for gutless vectors using episomal or stable expression of helper genomes. Additionally, the use of adeno-associated viruses encoding either conventional soluble VEGF receptors or new variants with superior pharmacokinetic properties is described.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2004
- Accession Number
- ADA423678
Entities
People
- Calvin J. Kuo
Organizations
- Stanford University