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.
Bibliographical noteFunding Information:
We thank Blanca Luena for technical assistance. FAM was supported by pre-doctoral fellowship (FI) UAB2006-00271 granted by the Universitat Autònoma de Barcelona. This work was supported by BIO2008-04692-Co3-01 from the Ministerio de Ciencia y Tecnología of the Government of Spain (RA), EU 6th FP research contract 18700 (Theragpox, RA), 2005 SGR 00727 from the Departament d’Universitats, Recerca I Societat de la Informació of the Generalitat de Catalunya and by Mutua Madrileña Medical Research Foundation. RA belongs to the Network of Cooperative Research on Cancer (C03-10), Instituto de Salud Carlos III of the Ministerio de Sanidad y Consumo, Government of Spain.
- canine adenovirus
- carrier cells
- oncolytic virus