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Designing Adenoviral Vectors for Tumor-Specific Targeting

  • Ramon AlemanyEmail author
Protocol
Part of the Methods in Molecular Biology™ book series (MIMB, volume 542)

Summary

Adenovirus provides an attractive candidate tool to destroy tumor cells. However, to fulfill the expectations, selective targeting of tumor cells is mandatory. This chapter reviews critical aspects in the design of tumor-targeted adenovirus vectors and oncolytic adenoviruses. The review focuses on genetic modifications of capsid and regulatory genes that can enhance the therapeutic index of these agents after systemic administration. Selectivity will be considered at different levels: biodistribution selectivity of the injected virus particles, transductional selectivity defined as cell receptor interactions and trafficking that lead to virus gene expression, transcriptional selectivity by means of tumor-selective promoters, and mutation-rescue selectivity to achieve selective replication. Proper assays to analyze selectivity at these different levels are discussed. Finally, mutations and transgenes that can enhance the potency and efficacy of tumor-targeted adenoviruses from virocentric or immunocentric points of view will be presented.

Keywords

Adenovirus oncolytic targeting tumor vector 

Notes

Acknowledgments

I thank the collaborative effort of the Virus Therapy Group at the Institut Català d?Oncologia involved in the author’s results mentioned herein. Special thanks to Manel Cascallo and Juan Fueyo for their close collaboration. Thanks to Cristina Balague for critical reading of the manuscript. The author is supported by Bio2005-08682-C03-01 from the Ministerio de Ciencia y Tecnología of the Government of Spain, the EU 6th FP research contract 18700 (Theradpox, RA), and the Network of Cooperative Research on Cancer (C03-10), Instituto de Salud Carlos III of the Ministerio de Sanidad y Consumo, Government of Spain.

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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Translational Research LaboratoryCatalan Institute of OncologyBarcelonaSpain

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