The addition of adenovirus type 5 region E3 enables calydon virus 787 to eliminate distant prostate tumor xenografts.
CV787, a novel highly prostate-specific replication-competent adenovirus with improved efficacy, was constructed. CV787 contains the prostate-specific rat probasin promoter, driving the adenovirus type 5 (Ad5) E1A gene, and the human prostate-specific enhancer/promoter, driving the E1B gene. To improve efficacy, we constructed CV787 such that it also contains the entire Ad5 E3 region. CV787 replicates in prostate-specific antigen (PSA)+ cells as well as wild-type adenovirus, but in PSA- cells, CV787 replicates 10(4)-10(5) times less efficiently. CV787 destroys PSA+ prostate cancer cells 10,000 times more efficiently than PSA- cells. Incorporation of the Ad5 E3 region significantly improves the target cell killing ability or efficacy of CV787. In nu/nu mice carrying s.c. LNCaP xenografts, a single i.v. tail vein injection of CV787 eliminates 300-mm3 tumors within 4 weeks. CV787 could be a powerful therapeutic for human metastatic prostate cancer.
Yu
D C
DC
Calydon, Inc., Sunnyvale, California 94089, USA.
Chen
Y
Y
Seng
M
M
Dilley
J
J
Henderson
D R
DR
D000256:Adenoviridae / Q000235:genetics*; D000727:Androgen-Binding Protein / Q000235:genetics*; D000818:Animals; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000628:therapy*; D051381:Rats; D014183:Transplantation, Heterologous; D014779:Virus Replication
D000727:Androgen-Binding Protein; C027519:probasin; D017430:Prostate-Specific Antigen