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Virotherapy of Canine Tumors with Oncolytic Vaccinia Virus GLV-1h109 Expressing an Anti-VEGF Single-Chain Antibody

Please always quote using this URN: urn:nbn:de:bvb:20-opus-130039
  • Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for cancer therapy. We have previously reported that oncolytic vaccinia virus strains expressing an anti-VEGF (Vascular Endothelial Growth Factor) single-chain antibody (scAb) GLAF-1 exhibited significant therapeutic efficacy for treatment of human tumor xenografts. Here, we describe the use of oncolytic vaccinia virus GLV-1h109 encoding GLAF-1 for canine cancer therapy. In this study we analyzed the virus-mediated delivery and production of scAb GLAF-1 andVirotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for cancer therapy. We have previously reported that oncolytic vaccinia virus strains expressing an anti-VEGF (Vascular Endothelial Growth Factor) single-chain antibody (scAb) GLAF-1 exhibited significant therapeutic efficacy for treatment of human tumor xenografts. Here, we describe the use of oncolytic vaccinia virus GLV-1h109 encoding GLAF-1 for canine cancer therapy. In this study we analyzed the virus-mediated delivery and production of scAb GLAF-1 and the oncolytic and immunological effects of the GLV-1h109 vaccinia virus strain against canine soft tissue sarcoma and canine prostate carcinoma in xenograft models. Cell culture data demonstrated that the GLV-1h109 virus efficiently infect, replicate in and destroy both tested canine cancer cell lines. In addition, successful expression of GLAF-1 was demonstrated in virus-infected canine cancer cells and the antibody specifically recognized canine VEGF. In two different xenograft models, the systemic administration of the GLV-1h109 virus was found to be safe and led to anti-tumor and immunological effects resulting in the significant reduction of tumor growth in comparison to untreated control mice. Furthermore, tumor-specific virus infection led to a continued production of functional scAb GLAF-1, resulting in inhibition of angiogenesis. Overall, the GLV-1h109-mediated cancer therapy and production of immunotherapeutic anti-VEGF scAb may open the way for combination therapy concept i.e. vaccinia virus mediated oncolysis and intratumoral production of therapeutic drugs in canine cancer patients.show moreshow less

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Metadaten
Author: Sandeep S. Patil, Ivaylo Gentschev, Marion Adelfinger, Ulrike Donat, Michael Hess, Stephanie Weibel, Ingo Nolte, Alexa Frentzen, Aladar A. Szalay
URN:urn:nbn:de:bvb:20-opus-130039
Document Type:Journal article
Faculties:Fakultät für Biologie / Rudolf-Virchow-Zentrum
Fakultät für Chemie und Pharmazie / Lehrstuhl für Biochemie
Language:English
Parent Title (English):PLoS One
Year of Completion:2012
Volume:7
Issue:10
Pagenumber:e47472
Source:PLoS ONE 7(10): e47472. doi:10.1371/journal.pone.0047472
DOI:https://doi.org/10.1371/journal.pone.0047472
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:angiogenesis; breast-tumors; cancer; endothelial growth-factor; microenvironment; microvascular density; model; nude-mice; pet dogs; therapy
Release Date:2016/11/25
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung