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Evaluation of adenovirus vectors containing serotype 35 fibers for tumor targeting

Abstract

There is growing evidence from in vitro studies that subgroup B adenoviruses (Ad) can overcome the limitations in safety and tumor transduction efficiency seen with commonly used subgroup C serotype 5-based vectors. In this study, we confirm that the expression level of the B-group Ad receptor, CD46, correlates with the grade of malignancy of cervical cancer in situ. We also demonstrate the in vivo properties of Ad5-based vectors that contain the B-group Ad serotype 35 fiber (Ad5/35) in transgenic mice that express CD46 in a pattern and at a level similar to humans. Upon intravenous and intraperitoneal injection, an Ad5/35 vector did not efficiently transduce normal tissue, but was able to target metastatic or intraperitoneal tumors that express CD46 at levels comparable to human tumors. When an oncolytic Ad5/35-based vector was employed, in both tumor models antitumor effects were observed. Furthermore, injection of Ad5/35 vectors into CD46 transgenic mice caused less innate toxicity than Ad5 vectors. Our data demonstrate that Ad vectors that target CD46 offer advantages over Ad5-based vectors for treatment of cancer.

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Acknowledgements

We thank Steve Roffler and Daniel Stone for critical discussions and Steve Hawes for help with statistical analyses. We are grateful to Branka Horvat for providing the transgenic mice. This study was supported by NIH Grants CA080192, HLA078836 and HL-00-008 and grants from the Doris Duke and Avon Charitable Foundations.

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Correspondence to A Lieber.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website (http://www.nature.com/cgt.

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Ni, S., Gaggar, A., Di Paolo, N. et al. Evaluation of adenovirus vectors containing serotype 35 fibers for tumor targeting. Cancer Gene Ther 13, 1072–1081 (2006). https://doi.org/10.1038/sj.cgt.7700981

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