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Статья
Targeting an Oncolytic Influenza A Virus to Tumor Tissue by Elastase
2021
Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs) containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA), which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site. We chose this cleavage site because elastase is expressed in the tumor microenvironment. Moreover, the exchange of the cleavage site previously has been shown to attenuate viral growth in lungs. Newly generated elastase-activated influenza viruses (AE viruses) grew to similar titers in tumor cells as the trypsin-activated counterparts (AT viruses). Intratumoral injection of AE viruses into syngeneic B16f1 melanoma-derived tumors in mice reduced tumor growth similar to AT viruses and had a better therapeutic effect in heterologous human PANC-1-derived tumors. Therefore, the introduction of the attenuation marker “elastase cleavage site” in viral HA allows for safe, effective oncolytic virus therapy. © 2017 The Authors
Цитирование
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Версии
- 1. Version of Record от 2021-04-27
Метаданные
Название журнала
- Molecular Therapy - Oncolytics
Том
- 7
Страницы
- 37-44
Ключевые слова
- elastase; leukocyte elastase; live vaccine; nonstructural protein 1; oncolytic influenza a virus; oncolytic virus; serine proteinase; trypsin; unclassified drug; virus hemagglutinin; virus vector; animal cell; animal experiment; animal model; Article; Avian encephalomyelitis enterovirus; B16-F1 cell line; cancer tissue; controlled study; drug targeting; female; gene deletion; human; human cell; Influenza A virus; intratumoral drug administration; lung parenchyma; mouse; nonhuman; oncolytic virotherapy; PANC-1 cell line; priority journal; protein cleavage; protein expression; therapy effect; tumor growth; tumor microenvironment; virogenesis; virus entry; virus replication
Издатель
- Cell Press
Тип документа
- journal article
Тип лицензии Creative Commons
- CC
Правовой статус документа
- Свободная лицензия
Источник
- scopus
