Anti-Angiogenic Gene Therapy of Prostate Cancer With Lentiviral Vectors
Abstract
Tumor progression induces the growth of endothelial cells by releasing angiogenic factors. This is accompanied by down-regulation of local tissue inhibitors of endothelian cell proliferation such as angiostatin and endostatin. Both proteins target normal endothelial cells and effectively regress large tumors in animals. However, animal studies demonstrate that an effective treatment requires long-term administration of angiogenesis inhibitors. Thus, delivery of angiogenesis inhibitor genes to tumor sites should increase local concentration of these proteins, leading to the retardation of tumor progression and metastasis. During the past fiscal year, we have generated two HIV vectors containing the endostatin and angiostatin cDNA. Human fibroblasts transduced with these vectors proliferated normally whereas the proliferation of primary HUVEC was inhibited by the transduction. For efficient gene expression in prostate cancer cells, we have generated HIV vectors containing the GFP gene controlled by the CMV fE promoter, the LTR from SFFV and the ubiquitin C promoter. We will determine the level of (3FP expression from these three promoters in human prostate cancer cell lines.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA410315
Entities
People
- Jiing-kuan Yee
Organizations
- City of Hope National Medical Center