TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling

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http://hdl.handle.net/10138/316189

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Heiniö , C , Havunen , R , Santos , J , de Lint , K , Cervera-Carrascon , V , Kanerva , A & Hemminki , A 2020 , ' TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling ' , Cells , vol. 9 , no. 4 , 798 . https://doi.org/10.3390/cells9040798

Title: TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling
Author: Heiniö, Camilla; Havunen, Riikka; Santos, Joao; de Lint, Klaas; Cervera-Carrascon, Victor; Kanerva, Anna; Hemminki, Akseli
Contributor: University of Helsinki, TRIMM - Translational Immunology Research Program
University of Helsinki, Department of Pathology
University of Helsinki, Department of Pathology
University of Helsinki, Research Programs Unit
University of Helsinki, Department of Oncology
Date: 2020-04
Language: eng
Number of pages: 13
Belongs to series: Cells
ISSN: 2073-4409
URI: http://hdl.handle.net/10138/316189
Abstract: 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.
Subject: aenovirus
virotherapy
immunotherapy
AIM2
oncolytic virus
TILT-123
immunological cell death
DAMP
PAMP
NF-KAPPA-B
TUMOR-INFILTRATING LYMPHOCYTES
NECROSIS-FACTOR-ALPHA
AIM2 INFLAMMASOME
DENDRITIC CELLS
CANCER
INTERLEUKIN-2
MATURATION
VIABILITY
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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