Abstract

Keywords

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

Juan Fueyo¹, Candelaria Gomez-Manzano¹, Ramon Alemany¹, Polly SY Lee¹, Timothy J McDonnell², Paraskevi Mitlianga¹, Yue-Xi Shi¹, V A Levin¹, W K Alfred Yung¹ & Athanassios P Kyritsis¹

Correspondence to: Juan Fueyo, Department of Neuro-Oncology, Box 100, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, TX 77030, USA

Effective anti cancer strategies necessitate the use of agents that target tumor cells rather than normal tissues. In this study, we constructed a tumor-selective adenovirus, 24, that carries a 24-bp deletion in the E1A region responsible for binding Rb protein. Immunoprecipitation analyses verified that this deletion rendered 24 unable to bind the Rb protein. However, titration experiments in 293 cells demonstrated that the 24 adenovirus could replicate in and lyse cancer cells with great efficiency. Lysis of most human glioma cells was observed within 10 – 14 days after infection with 24 at 10 PFU/cell. In vivo, a single dose of the 24 virus 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 fibroblasts or cancer cells with restored Rb activity were resistant to the 24 adenovirus. These results suggest that the E1A-mutant 24 adenovirus may be clinically and therapeutically useful against gliomas and possibly other cancers with disrupted Rb pathway. Oncogene (2000) 19, 2 – 12.

^© Macmillan Publishers Ltd 2000