Tumor Restrictive Gene Therapy for Metastatic Prostate Cancer
Final rept. 15 Nov 1999-14 Nov 2002
INDIANA UNIV INDIANAPOLIS
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The purpose of this proposal is to evaluate the ability of a replication-restrictive adenovirusAd-OC-Ela to specifically target and lyse cells of an androgen independent prostate cancer osseous metastasis, which account for a majority of the morbidity and mortality experienced by men with prostate cancer. The scope of this project is to perform the studies outlined in the proposal to prove the hypothesis that a conditional replication under the guidance of the osteocalcin promoter can exert a prostate cancer-specific cell kill in well defined pre-clinical models of human androgen independent prostate cancer metastases. Specific Aim I was designed to evaluate the in vitro ability of Ad-OC-Ela to specifically lyse human androgen independent prostate cancer cells and demonstrated up to a 100 fold killing differential favoring OC cell lines LNCaP, C4-2, PC-3 and over OC- cell lines LOVO, PrSC. Specific Aim II evaluates the growth inhibition of human prostate cancer xenografts after intralesional or systemic administration of Ad-OC-Ela, as well as, the tissue distribution and toxicity profile after administration. Ad-OC-Ela has demonstrated the ability to destroy human xenografts of both androgen-dependent and androgen-independent with limited toxicity.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research