Genetic Radiotherapy of Prostate Cancer
Abstract
A goal of this proposal is to achieve a high intratumoral concentration of 5-fluorouracil (5-FU) via molecular chemotherapy employing genetically modified adenoviral (Ad) vectors encoding the genes for somatostatin receptor subtype 2 (SSTr2) and cytosine deaminase (CD) which converts the prodrug 5-fluorocytosine (5-FC) to 5-FU under control of the cyclooxygenase-2 (Cox-2) tumor-specific promoter. The purpose of Specific Aim 1 was to develop, validate, and evaluate genetically modified Ad vectors that will increase expression levels of both SSTr2 and CD. We proposed to initially evaluate two novel two-gene Ad vectors: (1) a native fiber Ad (AdCMVCDCMVSSTr2) and (2) Ad under control of the Cox-2 promoter expressing CD and SSTr2. We have produced several vectors including AdCox-2LCDCox-2LS STr2, AdCox-2LS STr2Cox-2LCD, AdRGDCox- 2LCDCox-2LSSTr2, and AdRGDCox-2LCDCox-2LSSTr2. The vectors we developed were tested for SSTr2 and CD expression employing membrane receptor binding in vitro with 125I-somatostatin and 99mTc-P2O45 that binds to SSTr2, conversion of 5-FC to 5-FU, and cytotoxicity against Ad infected cells in the presence of 5-FC. The vectors were evaluated in vivo for SSTr2 expression and CD expression. Efforts are continuing to produce ROD modified vectors expressing CD and SSTr2 under control of the Cox-2L promoter to be used for therapy in local and metastatic models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2003
- Accession Number
- ADA422767
Entities
People
- Donald J. Buchsbaum
Organizations
- University of Alabama