title: Preclinical evaluation of oncolytic vaccinia virus for therapy of canine soft tissue sarcoma.
abstract: Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for canine cancer therapy. In this study we describe the establishment of an in vivo model of canine soft tissue sarcoma (CSTS) using the new isolated cell line STSA-1 and the analysis of the virus-mediated oncolytic and immunological effects of two different Lister VACV LIVP1.1.1 and GLV-1h68 strains against CSTS. Cell culture data demonstrated that both tested VACV strains efficiently infected and destroyed cells of the canine soft tissue sarcoma line STSA-1. In addition, in our new canine sarcoma tumor xenograft mouse model, systemic administration of LIVP1.1.1 or GLV-1h68 viruses led to significant inhibition of tumor growth compared to control mice. Furthermore, LIVP1.1.1 mediated therapy resulted in almost complete tumor regression and resulted in long-term survival of sarcoma-bearing mice. The replication of the tested VACV strains in tumor tissues led to strong oncolytic effects accompanied by an intense intratumoral infiltration of host immune cells, mainly neutrophils. These findings suggest that the direct viral oncolysis of tumor cells and the virus-dependent activation of tumor-associated host immune cells could be crucial parts of anti-tumor mechanism in STSA-1 xenografts. In summary, the data showed that both tested vaccinia virus strains and especially LIVP1.1.1 have great potential for effective treatment of CSTS.
authors.affiliation: Genelux Corporation, San Diego Science Center, San Diego, California, United States of America.
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Gentschev
authors.forename: Marion
authors.initials: M
authors.lastname: Adelfinger
authors.forename: Rafael
authors.initials: R
authors.lastname: Josupeit
authors.forename: Stephan
authors.initials: S
authors.lastname: Rudolph
authors.forename: Klaas
authors.initials: K
authors.lastname: Ehrig
authors.forename: Ulrike
authors.initials: U
authors.lastname: Donat
authors.forename: Stephanie
authors.initials: S
authors.lastname: Weibel
authors.forename: Nanhai G
authors.initials: NG
authors.lastname: Chen
authors.forename: Yong A
authors.initials: YA
authors.lastname: Yu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Martin
authors.initials: M
authors.lastname: Heisig
authors.forename: Douglas
authors.initials: D
authors.lastname: Thamm
authors.forename: Jochen
authors.initials: J
authors.lastname: Stritzker
authors.forename: Amy
authors.initials: A
authors.lastname: Macneill
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary / Q000662:veterinary; D045744:Cell Line, Tumor; D004285:Dogs; D051379:Mice; D019042:Muscle Neoplasms / Q000628:therapy / Q000662:veterinary*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000502:physiology; D012509:Sarcoma / Q000473:pathology / Q000628:therapy / Q000662:veterinary*; D012983:Soft Tissue Neoplasms / Q000628:therapy / Q000662:veterinary*; D014616:Vaccinia virus / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology; D023041:Xenograft Model Antitumor Assays