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TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling
Cancer Gene Therapy Group, Faculty of Medicine, TRIMM, University of Helsinki, Haartmaninkatu 3, 00290 Helsinki, Finland
TILT Biotherapeutics Ltd., Haartmaninkatu 3, 00290 Helsinki, Finland
Amsterdam UMC, Clinical Genetics, Section Oncogenetics, Cancer Center Amsterdam, De Boelelaan 1117, 1118, 1081 HV Amsterdam, The Netherlands
Department of Obstetrics and Gynecology, Helsinki University Hospital, Haartmaninkatu 2, 00290 Helsinki, Finland
Helsinki University Hospital Comprehensive Cancer Center, Paciuksenkatu 3, 00290 Helsinki, Finland
Author to whom correspondence should be addressed.
Cells 2020, 9(4), 798; https://doi.org/10.3390/cells9040798 (registering DOI)
Received: 28 February 2020 / Revised: 23 March 2020 / Accepted: 24 March 2020 / Published: 26 March 2020
In order to break tumor resistance towards traditional treatments, we investigate the response of tumor and immune cells to a novel, cytokine-armed oncolytic adenovirus: Ad5/3-d24-E2F-hTNFa-IRES-hIL2 (also known as TILT-123 and OAd.TNFa-IL2). There are several pattern recognition receptors (PRR) that might mediate adenovirus-infection recognition. However, the role and specific effects of each PRR on the tumor microenvironment and treatment outcome remain unclear. Hence, the aim of this study was to investigate the effects of OAd.TNFa-IL2 infection on PRR-mediated danger- and pathogen-associated molecular pattern (DAMP and PAMP, respectively) signaling. In addition, we wanted to see which PRRs mediate an antitumor response and are therefore relevant for optimizing this virotherapy. We determined that OAd.TNFa-IL2 induced DAMP and PAMP release and consequent tumor microenvironment modulation. We show that the AIM2 inflammasome is activated during OAd.TNFa-IL2 virotherapy, thus creating an immunostimulatory antitumor microenvironment.
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