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

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dc.contributor.author Cervera-Carrascon, Victor
dc.contributor.author Quixabeira, Dafne C. A.
dc.contributor.author Santos, Joao M.
dc.contributor.author Havunen, Riikka
dc.contributor.author Milenova, Ioanna
dc.contributor.author Verhoeff, Jan
dc.contributor.author Heinio, Camilla
dc.contributor.author Zafar, Sadia
dc.contributor.author Garcia-Vallejo, Juan J.
dc.contributor.author van Beusechem, Victor W.
dc.contributor.author de Gruijl, Tanja D.
dc.contributor.author Kalervo, Aino
dc.contributor.author Sorsa, Suvi
dc.contributor.author Kanerva, Anna
dc.contributor.author Hemminki, Akseli
dc.date.accessioned 2021-09-17T11:38:02Z
dc.date.available 2021-09-17T11:38:02Z
dc.date.issued 2021-07-23
dc.identifier.citation 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
dc.identifier.other PURE: 168543211
dc.identifier.other PURE UUID: 43ebdb1c-d946-4dfd-9110-57c4097c8045
dc.identifier.other WOS: 000681630500001
dc.identifier.uri http://hdl.handle.net/10138/334437
dc.description.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. en
dc.format.extent 12
dc.language.iso eng
dc.relation.ispartof Frontiers in Immunology
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject cancer immunotherapy
dc.subject oncolytic virus
dc.subject adenovirus
dc.subject checkpoint inhibitor resistance
dc.subject tumor microenvironment
dc.subject IMMUNE CHECKPOINT INHIBITORS
dc.subject NECROSIS-FACTOR-ALPHA
dc.subject T-CELL THERAPY
dc.subject ACQUIRED-RESISTANCE
dc.subject ONCOLYTIC VIRUSES
dc.subject PD-1 BLOCKADE
dc.subject COMBINATION
dc.subject IMPROVES
dc.subject LANDSCAPE
dc.subject 3111 Biomedicine
dc.title Adenovirus Armed With TNFa and IL2 Added to aPD-1 Regimen Mediates Antitumor Efficacy in Tumors Refractory to aPD-1 en
dc.type Article
dc.contributor.organization Department of Pathology
dc.contributor.organization TRIMM - Translational Immunology Research Program
dc.contributor.organization Faculty of Medicine
dc.contributor.organization Research Programs Unit
dc.contributor.organization Medicum
dc.contributor.organization HUS Comprehensive Cancer Center
dc.contributor.organization Genome-Scale Biology (GSB) Research Program
dc.contributor.organization HUS Gynecology and Obstetrics
dc.contributor.organization Akseli Eetu Hemminki / Principal Investigator
dc.contributor.organization Clinicum
dc.contributor.organization Department of Obstetrics and Gynecology
dc.contributor.organization Department of Oncology
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3389/fimmu.2021.706517
dc.relation.issn 1664-3224
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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