Abscopal Effect in Non-injected Tumors Achieved with Cytokine-Armed Oncolytic Adenovirus

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http://hdl.handle.net/10138/292423

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Havunen , R , Santos , J M , Sorsa , S , Rantapero , T , Lumen , D , Siurala , M , Airaksinen , A J , Cervera-Carrascon , V , Tähtinen , S , Kanerva , A & Hemminki , A 2018 , ' Abscopal Effect in Non-injected Tumors Achieved with Cytokine-Armed Oncolytic Adenovirus ' , Molecular Therapy - Oncolytics , vol. 11 , pp. 109-121 . https://doi.org/10.1016/j.omto.2018.10.005

Title: Abscopal Effect in Non-injected Tumors Achieved with Cytokine-Armed Oncolytic Adenovirus
Author: Havunen, Riikka; Santos, Joao M.; Sorsa, Suvi; Rantapero, Tommi; Lumen, Dave; Siurala, Mikko; Airaksinen, Anu J.; Cervera-Carrascon, Victor; Tähtinen, Siri; Kanerva, Anna; Hemminki, Akseli
Contributor organization: Department of Oncology
Clinicum
Faculty of Medicine
University of Helsinki
Department of Pathology
Medicum
Tracers in Molecular Imaging (TRIM)
Department of Chemistry
Helsinki In Vivo Animal Imaging Platform (HAIP)
Akseli Eetu Hemminki / Principal Investigator
Department of Obstetrics and Gynecology
HUS Comprehensive Cancer Center
Date: 2018-12-21
Language: eng
Number of pages: 13
Belongs to series: Molecular Therapy - Oncolytics
ISSN: 2372-7705
DOI: https://doi.org/10.1016/j.omto.2018.10.005
URI: http://hdl.handle.net/10138/292423
Abstract: Cancer treatment with local administration of armed oncolytic viruses could potentially induce systemic antitumor effects, or the abscopal effect, as they self-amplify in tumors, induce danger signaling, and promote tumor-associated antigen presentation. In this study, oncolytic adenovirus coding for human tumor necrosis factor alpha (TNF-alpha) and interleukin-2 (IL-2) Ad5/3-E2F-d24-hTNF-alpha-IRES-hIL-2 (also known as [a.k.a.] TILT-123) provoked antitumor efficacy in tumors that were injected with Ad5/3-E2F-d24-hTNF-alpha-IRES-hIL-2 and those that were left non-injected in the same animal. Importantly, the virus was able to travel to distant tumors. To dissect the effects of oncolysis and cytokines, we studied replication-incompetent viruses in mice. Systemic antitumor effects were similar in both models, highlighting the importance of the arming device. The cytokines induced positive changes in immune cell infiltrates and induced the expression of several immune-reaction-related genes in tumors. In addition, Ad5/3-E2F-d24-hTNF-alpha-IRES-hIL-2 was able to increase homing of adoptively transferred tumor-infiltrating lymphocytes into both injected and non-injected tumors, possibly mediated through chemokine expression. In summary, local treatment with Ad5/3-E2F-d24-hTNF-alpha-IRES-hIL-2 resulted in systemic antitumor efficacy by inducing immune cell infiltration and trafficking into both treated and untreated tumors. Moreover, the oncolytic adenovirus platform had superior systemic effects over replication-deficient vector through spreading into distant tumors.
Subject: NECROSIS-FACTOR-ALPHA
ADOPTIVE CELL THERAPY
NATURAL-KILLER-CELLS
DENDRITIC CELLS
CANCER-PATIENTS
OVARIAN-CANCER
NK CELLS
IMMUNOTHERAPY
INTERLEUKIN-2
MELANOMA
3122 Cancers
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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