Osteosarcoma cells as carriers to allow antitumor activity of canine oncolytic adenovirus in the presence of neutralizing antibodies
Alcayaga Miranda, Francisca Andrea (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Cascalló, Manel (Institut Català d'Oncologia)
Rojas Expósito, Juan José (Institut Català d'Oncologia)
Pastor Milán, Josep (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Alemany Bonastre, Ramon (Institut Català d'Oncologia)

Date:	2010
Abstract:	Osteosarcoma (OSA) is the most common bone tumor affecting the dog. The veterinary options for therapeutic management of OSA are limited and prognosis for such patients is poor. Oncolytic adenoviruses are attractive tools for experimental therapeutics as they can replicate and spread within tumors to directly induce tumor destruction. However, a major impediment to systemic oncolytic adenoviruses injection is the presence of pre-existing neutralizing antibodies (Nabs). In this study, we investigated the effect of a replication-selective canine adenovirus (OCCAV) to treat OSA in the presence of Nabs and the use of canine OSA cells as carrier vehicles for evading Nabs. Our systemic biodistribution data indicated that canine tumor cells could successfully reach the tumor site and deliver OCCAV to tumor cells in an immunized mice model. Furthermore, the use of carrier cells also reduced adenovirus uptake by the liver. Importantly, OCCAV alone was not effective to control tumor growth in a pre-immunized xenograft mouse model. On the contrary, systemic antitumoral activity of carrier-cell OCCAV was evident even in the presence of circulating antibodies, which is a relevant result from a clinical point of view. These findings are of direct translational relevance for the future design of canine clinical trials.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Càncer ; Teràpia genètica ; Gossos ; Malalties ; Oncologia veterinària ; Osteosarcoma ; Dog ; Carrier cells ; Canine adenovirus ; Oncolytic virus
Published in:	Cancer Gene Therapy, Vol. 17 Núm. 11 (Novembre 2010) , p. 792-802, ISSN 1476-5500

DOI: 10.1038/cgt.2010.36
PMID: 20671769

13 p, 1.0 MB

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