A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo

Effective anti cancer strategies necessitate the use of agents that target tumor cells rather than normal tissues, In this study, we constructed a tum or-selective adenovirus, Delta 24, that carries a 24-bp deletion in the E1A region responsible for binding Rb protein. Immunoprecipitation analyses ve rified that this deletion rendered Delta 24 unable to bind the Rb protein. However, titration experiments in 293 cells demonstrated that the Delta 24 adenovirus could replicate in and Iyse cancer cells with great efficiency. Lysis of most human glioma cells was observed within 10-14 days after infec tion with Delta 24 at 10 PFU/cell. In vivo, a single dose of the Delta 24 v irus induced a 66.3% inhibition (P<0.005) and multiple injections, an 83.8% inhibition (P<0.01) of tumor growth in nude mice. However, normal fibrobla sts or cancer cells with restored Rb activity were resistant to the Delta 2 4 adenovirus. These results suggest that the E1A-mutant Delta 24 adenovirus may be clinically and therapeutically useful against gliomas and possibly other cancers with disrupted Rb pathway.