Virotherapy of Canine Tumors with Oncolytic Vaccinia Virus GLV-1h109 Expressing an Anti-VEGF Single-Chain Antibody
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- 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.…
Autor(en): | Sandeep S. Patil, Ivaylo Gentschev, Marion Adelfinger, Ulrike Donat, Michael Hess, Stephanie Weibel, Ingo Nolte, Alexa Frentzen, Aladar A. Szalay |
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URN: | urn:nbn:de:bvb:20-opus-130039 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Biologie / Rudolf-Virchow-Zentrum |
Fakultät für Chemie und Pharmazie / Lehrstuhl für Biochemie | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | PLoS One |
Erscheinungsjahr: | 2012 |
Band / Jahrgang: | 7 |
Heft / Ausgabe: | 10 |
Seitenangabe: | e47472 |
Originalveröffentlichung / Quelle: | PLoS ONE 7(10): e47472. doi:10.1371/journal.pone.0047472 |
DOI: | https://doi.org/10.1371/journal.pone.0047472 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | angiogenesis; breast-tumors; cancer; endothelial growth-factor; microenvironment; microvascular density; model; nude-mice; pet dogs; therapy |
Datum der Freischaltung: | 25.11.2016 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung |