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

A Corrigendum to this article was published on 12 October 2000

Abstract

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, Δ24, that carries a 24-bp deletion in the E1A region responsible for binding Rb protein. Immunoprecipitation analyses verified that this deletion rendered Δ24 unable to bind the Rb protein. However, titration experiments in 293 cells demonstrated that the Δ24 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 Δ24 at 10 PFU/cell. In vivo, a single dose of the Δ24 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 Δ24 adenovirus. These results suggest that the E1A-mutant Δ24 adenovirus may be clinically and therapeutically useful against gliomas and possibly other cancers with disrupted Rb pathway.

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Acknowledgements

We gratefully acknowledge Christine Wogan (Department of Scientific Publications, The University of Texas M.D. Anderson Cancer Center (UTMDACC)) for her editorial assistance, Karen Ramirez (Department of Immunology, UTMDACC) for her contribution to the flow cytometry studies, and Jim Lemoine (Department of Medical Graphics, (UTMDACC) for his help in the design of the figures.

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Fueyo, J., Gomez-Manzano, C., Alemany, R. et al. A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene 19, 2–12 (2000). https://doi.org/10.1038/sj.onc.1203251

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