Journal
HUMAN GENE THERAPY
Volume 30, Issue 1, Pages 44-56Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2018.026
Keywords
adenovirus; ultrasound guided; bladder cancer; oncolytic; virotherapy; YB-1; MIBC
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Funding
- German Research Foundation (DFG) [HO-1482/7-1]
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Muscle-invasive bladder cancer represents approximately 25% of diagnosed bladder cancer cases and carries a significant risk of death. Oncolytic viruses are novel antitumor agents with the ability to selectively replicate and lyse tumor cells while sparing healthy tissue. We explored the efficiency of the oncolytic YB-1-selective adenovirus XVir-N-31 in vitro and in an orthotopic mouse model for bladder cancer by intramural injection under ultrasound guidance. We demonstrated that XVir-N-31 replicated in bladder cancer cells and induced a stronger immunogenic cell death than wild-type adenovirus by facilitating enhanced release of HMGB1 and exosomal Hsp70. The intratumoral delivery of XVir-N-31 by ultrasound guidance delayed tumor growth in an immunodeficient model, demonstrating the feasibility of this approach to deliver oncolytic viruses directly into the tumor.
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