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The chicken chorioallantoic membrane tumor assay as model for qualitative testing of oncolytic adenoviruses

Cancer Gene Therapy volume 19, pages 58–68 (2012)Cite this article

Abstract

Oncolytic adenoviruses are promising anticancer agents. To study and optimize their tumor-killing potency, genuine tumor models are required. Here we describe the use of the chicken chorioallantoic membrane (CAM) tumor model in studies on oncolytic adenoviral vectors. Suspensions of human melanoma, colorectal carcinoma and glioblastoma multiforme cell lines were grafted on the CAM of embryonated chicken eggs. All cell lines tested formed 5–10 mm size tumors, which recapitulated hallmarks of corresponding human specimens. Furthermore, melanoma tumors were injected with adenoviral vector-carrying gene encoding the fusion protein of parainfluenza virus type 5. This led to the induction of cell fusion and syncytia formation in the infected cells. At 6 days post-injection, histological and immunohistochemical analyses of tumor sections confirmed adenovirus replication and syncytia formation. These results demonstrate that the CAM model allows rapid assessment of oncolytic viruses in three-dimensional tumors. Hence, this model constitutes an easy and affordable system for preclinical characterization of viral oncolytic agents that may precede the mandatory process of animal testing. Application of this model will help reducing the use of human xenografts in mice for preclinical evaluation of oncolytic viruses and other anticancer agents.

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Acknowledgements

We thank B Bancel for precious technical assistance in immunohistochemistry, L Fanchi for his assistance with photography and Drs L Depaepe, F Ragage, S Isaac and A Vasiljevic for providing the human samples and for their help with interpreting histological sections. FD was supported by the Fondation René Touraine (France) and the Institut Servier (France), RCH and DKL were supported by the European Union through the 6th Framework Program GIANT (Contract No. 512087) and MRC was supported by a Contrat d’Interface grant from the Hospices Civils de Lyon (France) and by a grant from La Ligue Contre le Cancer (France).

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Author notes

  1. D Koppers-Lalic

    Present address: 7Current address: Department of Pathology, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.,

  2. F Durupt and D Koppers-Lalic: These two authors contributed equally to this work.

  3. R C Hoeben and M Rosa-Calatrava: These two authors contributed equally to this work.

Authors and Affiliations

  1. Laboratoire de Virologie, VirPath, CNRS FRE3011, Université Claude Bernard Lyon I, Faculté de Médecine RTH Laennec, Université de Lyon, Lyon, France

    F Durupt, O Terrier, B Lina & M Rosa-Calatrava

  2. Service de Dermatologie, Centre Hospitalier Lyon Sud, Université Lyon I, Pierre-Bénite, France

    F Durupt & L Thomas

  3. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

    F Durupt, D Koppers-Lalic, L Budel & R C Hoeben

  4. Laboratoire d’anatomie Pathologique, Centre Hospitalier Lyon Sud, Université Lyon I, Pierre-Bénite, France

    B Balme

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Correspondence to R C Hoeben or M Rosa-Calatrava.

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Durupt, F., Koppers-Lalic, D., Balme, B. et al. The chicken chorioallantoic membrane tumor assay as model for qualitative testing of oncolytic adenoviruses. Cancer Gene Ther 19, 58–68 (2012). https://doi.org/10.1038/cgt.2011.68

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