Adenovirus Armed With TNFa and IL2 Added to aPD-1 Regimen Mediates Antitumor Efficacy in Tumors Refractory to aPD-1

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Cervera-Carrascon , V , Quixabeira , D C A , Santos , J M , Havunen , R , Milenova , I , Verhoeff , J , Heinio , C , Zafar , S , Garcia-Vallejo , J J , van Beusechem , V W , de Gruijl , T D , Kalervo , A , Sorsa , S , Kanerva , A & Hemminki , A 2021 , ' Adenovirus Armed With TNFa and IL2 Added to aPD-1 Regimen Mediates Antitumor Efficacy in Tumors Refractory to aPD-1 ' , Frontiers in Immunology , vol. 12 , 706517 . https://doi.org/10.3389/fimmu.2021.706517

Title: Adenovirus Armed With TNFa and IL2 Added to aPD-1 Regimen Mediates Antitumor Efficacy in Tumors Refractory to aPD-1
Author: Cervera-Carrascon, Victor; Quixabeira, Dafne C. A.; Santos, Joao M.; Havunen, Riikka; Milenova, Ioanna; Verhoeff, Jan; Heinio, Camilla; Zafar, Sadia; Garcia-Vallejo, Juan J.; van Beusechem, Victor W.; de Gruijl, Tanja D.; Kalervo, Aino; Sorsa, Suvi; Kanerva, Anna; Hemminki, Akseli
Contributor organization: Department of Pathology
TRIMM - Translational Immunology Research Program
Faculty of Medicine
Research Programs Unit
Medicum
HUS Comprehensive Cancer Center
Genome-Scale Biology (GSB) Research Program
HUS Gynecology and Obstetrics
Akseli Eetu Hemminki / Principal Investigator
Clinicum
Department of Obstetrics and Gynecology
Department of Oncology
Date: 2021-07-23
Language: eng
Number of pages: 12
Belongs to series: Frontiers in Immunology
ISSN: 1664-3224
DOI: https://doi.org/10.3389/fimmu.2021.706517
URI: http://hdl.handle.net/10138/334437
Abstract: Immune checkpoint inhibitors such as anti-PD-1 have revolutionized the field of oncology over the past decade. Nevertheless, the majority of patients do not benefit from them. Virotherapy is a flexible tool that can be used to stimulate and/or recruit different immune populations. T-cell enabling virotherapy could enhance the efficacy of immune checkpoint inhibitors, even in tumors resistant to these inhibitors. The T-cell potentiating virotherapy used here consisted of adenoviruses engineered to express tumor necrosis factor alpha and interleukin-2 in the tumor microenvironment. To study virus efficacy in checkpoint-inhibitor resistant tumors, we developed an anti-PD-1 resistant melanoma model in vivo. In resistant tumors, adding virotherapy to an anti-PD-1 regimen resulted in increased survival (p=0.0009), when compared to anti-PD-1 monotherapy. Some of the animals receiving virotherapy displayed complete responses, which did not occur in the immune checkpoint-inhibitor monotherapy group. When adenoviruses were delivered into resistant tumors, there were signs of increased CD8 T-cell infiltration and activation, which - together with a reduced presence of M2 macrophages and myeloid-derived suppressor cells - could explain those results. T-cell enabling virotherapy appeared as a valuable tool to counter resistance to immune checkpoint inhibitors. The clinical translation of this approach could increase the number of cancer patients benefiting from immunotherapies.
Subject: cancer immunotherapy
oncolytic virus
adenovirus
checkpoint inhibitor resistance
tumor microenvironment
IMMUNE CHECKPOINT INHIBITORS
NECROSIS-FACTOR-ALPHA
T-CELL THERAPY
ACQUIRED-RESISTANCE
ONCOLYTIC VIRUSES
PD-1 BLOCKADE
COMBINATION
IMPROVES
LANDSCAPE
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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