GMCSF‐armed vaccinia virus induces an antitumor immune response. Issue 5 (10th July 2014)

• Record Type: Journal Article
• Authors: Parviainen, Suvi; Ahonen, Marko; Diaconu, Iulia; Kipar, Anja; Siurala, Mikko; Vähä‐Koskela, Markus; Kanerva, Anna; Cerullo, Vincenzo; Hemminki, Akseli
• Is Part Of: International journal of cancer. Volume 136:Issue 5(2015:Mar. 01)
• Page Start: 1065
• Page End: 1072
• Publication Date: 2014-07-10
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29068
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Oncolytic Western Reserve strain vaccinia virus selective for epidermal growth factor receptor pathway mutations and tumor‐associated hypermetabolism was armed with human granulocyte‐macrophage colony‐stimulating factor (GMCSF) and a tdTomato fluorophore. As the assessment of immunological responses to human transgenes is challenging in the most commonly used animal models, we used immunocompetent Syrian golden hamsters, known to be sensitive to human GMCSF and semipermissive to vaccinia virus. Efficacy was initially tested <italic>in vitro</italic> on various human and hamster cell lines and oncolytic potency of transgene‐carrying viruses was similar to unarmed virus. The hGMCSF‐encoding virus was able to completely eradicate subcutaneous pancreatic tumors in hamsters, and to fully protect the animals from subsequent rechallenge with the same tumor. Induction of specific antitumor immunity was also shown by <italic>ex vivo</italic> co‐culture experiments with hamster splenocytes. In addition, histological examination revealed increased infiltration of neutrophils and macrophages in GMCSF‐virus‐treated tumors. These findings help clarify the mechanism of action of GMCSF‐armed vaccinia viruses undergoing clinical trials.</p> </abstract>