Cowpox Virus: A New and Armed Oncolytic Poxvirus
| Autor: | Stéphane Bertagnoli, Johann Foloppe, Marine Ricordel, Delphine Antoine, Pascale Cordier, Sandrine Cochin, Christelle Camus-Bouclainville, Eric Quemeneur, Nathalie Sfrontato, Philippe Erbs, Christelle Pichon, Caroline Tosch |
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| Přispěvatelé: | Transgene SA, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Virologie Cowpox Médecine humaine et pathologie [SDV.CAN]Life Sciences [q-bio]/Cancer Biology lcsh:RC254-282 Virus 03 medical and health sciences Virology medicine Cytotoxic T cell Pharmacology (medical) Cancer Cowpox virus armed Suicide gene lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease cowpox 3. Good health Oncolytic virus 030104 developmental biology Oncology oncolytic Thymidine kinase [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Molecular Medicine Oncolytic Virus Therapy Original Article Human health and pathology [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Molecular Therapy-Oncolytics Molecular Therapy-Oncolytics, Elsevier, 2017, 7, pp.1-11. ⟨10.1016/j.omto.2017.08.003⟩ Molecular Therapy: Oncolytics, Vol 7, Iss, Pp 1-11 (2017) Molecular Therapy Oncolytics (7), 1-11. (2017) Molecular Therapy Oncolytics |
| ISSN: | 2372-7705 |
| Popis: | Oncolytic virus therapy has recently been recognized as a promising new therapeutic approach for cancer treatment. In this study, we are proposing for the first time to evaluate the in vitro and in vivo oncolytic capacities of the Cowpox virus (CPXV). To improve the tumor selectivity and oncolytic activity, we developed a thymidine kinase (TK)-deleted CPXV expressing the suicide gene FCU1, which converts the non-toxic prodrug 5-fluorocytosine (5-FC) into cytotoxic 5-fluorouracil (5-FU) and 5-fluorouridine-5′-monophosphate (5-FUMP). This TK-deleted virus replicated efficiently in human tumor cell lines; however, it was notably attenuated in normal primary cells, thus displaying a good therapeutic index. Furthermore, this new recombinant poxvirus rendered cells sensitive to 5-FC. In vivo, after systemic injection in mice, the TK-deleted variant caused significantly less mortality than the wild-type strain. A biodistribution study demonstrated high tumor selectivity and low accumulation in normal tissues. In human xenograft models of solid tumors, the recombinant CPXV also displayed high replication, inducing relevant tumor growth inhibition. This anti-tumor effect was improved by 5-FC co-administration. These results demonstrated that CPXV is a promising oncolytic vector capable of expressing functional therapeutic transgenes. Keywords: cowpox, oncolytic, armed |
| Databáze: | OpenAIRE |
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