The oncolytic Adenovirus XVir-N-31 as a novel therapy in muscle-invasive bladder cancer
Eva Lichtenegger, Florestan Koll, Helena Haas, Klaus Mantwill, Klaus-Peter Janssen, Melanie Laschinger, Jürgen Gschwend, Katja Steiger, Peter Black, Igor Moskalev, Roman Nawroth, Per Sonne HolmHuman Gene Therapy2018
Muscle‐invasive bladder cancer represents approximately 25% of patients diagnosed with bladder cancer and carries a significant risk of death. Oncolytic viruses (OV) are novel antitumor agents with the ability to selectively replicate and lyse tumor cells while sparing healthy tissue. Thus, 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 replicates in bladder cancer cells and induced a stronger immunogenic cell death than adenovirus wildtype 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.