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Designing Adenoviral Vectors for Tumor-Specific Targeting

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Gene Therapy of Cancer

Part of the book series: Methods in Molecular Biology™ ((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.

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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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Authors and Affiliations

  1. Translational Research Laboratory, Catalan Institute of Oncology, Av Gran Via s/n Km2, 7, 08907 L?Hospitalet de Llobregat, Barcelona, Spain

    Ramon Alemany

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  1. Ramon Alemany
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Correspondence to Ramon Alemany .

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Editors and Affiliations

  1. Molecular Medicine (MDC), Max Delbrück Center for, Robert-Rössle-Str. 10, Berlin, 13125, Germany

    Wolfgang Walther

  2. Molecular Medicine (MDC), Max Delbrück Center for, Robert-Rössle-Str. 10, Berlin, 13125, Germany

    Ulrike S. Stein

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

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Alemany, R. (2009). Designing Adenoviral Vectors for Tumor-Specific Targeting. In: Walther, W., Stein, U. (eds) Gene Therapy of Cancer. Methods in Molecular Biology™, vol 542. Humana Press. https://doi.org/10.1007/978-1-59745-561-9_2

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  • DOI: https://doi.org/10.1007/978-1-59745-561-9_2

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-934115-85-5

  • Online ISBN: 978-1-59745-561-9

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