GMCSF-armed vaccinia virus induces an antitumor immune response
| Autor: | Parviainen, S, Ahonen, M, Diaconu, I, Kipar, A, Siurala, M, Vähä-Koskela, M, Kanerva, A, Cerullo, V, Hemminki, A |
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| Přispěvatelé: | Parviainen, Suvi, Ahonen, Marko, Diaconu, Iulia, Kipar, Anja, Siurala, Mikko, Vähä-Koskela, Marku, Kanerva, Anna, Cerullo, Vincenzo, Hemminki, Akseli, University of Zurich, Hemminki, A |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Xenograft Model Antitumor Assay Macrophage Immunoenzyme Technique 10184 Institute of Veterinary Pathology Cercopithecus aethiop Real-Time Polymerase Chain Reaction Virus Replication Cell Movement Cricetinae 1306 Cancer Research RNA Messenger Coculture Technique Cells Cultured Cell Proliferation Oncolytic Virotherapy Mesocricetu Oncolytic vaccinia viru Animal Reverse Transcriptase Polymerase Chain Reaction Medicine (all) Pancreatic Neoplasm Granulocyte-Macrophage Colony-Stimulating Factor Vaccinia viru T-Lymphocyte Oncology DNA Viral Vero Cell 570 Life sciences biology 2730 Oncology Immunotherapy GMCSF Human |
| Zdroj: | International Journal of Cancer |
| ISSN: | 0020-7136 |
| DOI: | 10.1002/ijc.29068 |
| Popis: | 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 in vitro 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 ex vivo 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. |
| Databáze: | OpenAIRE |
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