title: Lister vaccine strain of vaccinia virus armed with the endostatin-angiostatin fusion gene: an oncolytic virus superior to dl1520 (ONYX-015) for human head and neck cancer.
abstract: Oncolytic viral therapy represents a promising strategy for the treatment of head and neck squamous cell carcinoma (HNSCC), with dl1520 (ONYX-015) the most widely used oncolytic adenovirus in clinical trials. This study aimed to determine the effectiveness of the Lister vaccine strain of vaccinia virus as well as a vaccinia virus armed with the endostatin-angiostatin fusion gene (VVhEA) as a novel therapy for HNSCC and to compare them with dl1520. The potency and replication of the Lister strain and VVhEA and the expression and function of the fusion protein were determined in human HNSCC cells in vitro and in vivo. Finally, the efficacy of VVhEA was compared with dl1520 in vivo in a human HNSCC model. The Lister vaccine strain of vaccinia virus was more effective than the adenovirus against all HNSCC cell lines tested in vitro. Although the potency of VVhEA was attenuated in vitro, the expression and function of the endostatin-angiostatin fusion protein was confirmed in HNSCC models both in vitro and in vivo. This novel vaccinia virus (VVhEA) demonstrated superior antitumor potency in vivo compared with both dl1520 and the control vaccinia virus. This study suggests that the Lister strain vaccinia virus armed with an endostatin-angiostatin fusion gene may be a potential therapeutic agent for HNSCC.
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary of London, London EC1M 6BQ, United Kingdom.
authors.forename: James R
authors.initials: JR
authors.lastname: Tysome
authors.forename: Pengju
authors.initials: P
authors.lastname: Wang
authors.forename: Ghassan
authors.initials: G
authors.lastname: Alusi
authors.forename: Arnaud
authors.initials: A
authors.lastname: Briat
authors.forename: Rathi
authors.initials: R
authors.lastname: Gangeswaran
authors.forename: Jiwei
authors.initials: J
authors.lastname: Wang
authors.forename: Vipul
authors.initials: V
authors.lastname: Bhakta
authors.forename: Istvan
authors.initials: I
authors.lastname: Fodor
authors.forename: Nick R
authors.initials: NR
authors.lastname: Lemoine
authors.forename: Yaohe
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D043168:Angiostatins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D003588:Cytopathogenic Effect, Viral; D043169:Endostatins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D014616:Vaccinia virus / Q000235:genetics*; D014765:Viral Vaccines; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D043169:Endostatins; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines; C464532:dl1520; D043168:Angiostatins