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

Bibliographic Details
Title:	Adenovirus Armed With TNFa and IL2 Added to aPD-1 Regimen Mediates Antitumor Efficacy in Tumors Refractory to aPD-1
Authors:	Cervera-Carrascon, Victor, Quixabeira, Dafne C. A., Santos, Joao M., Havunen, Riikka, Milenova, Ioanna, Verhoeff, Jan, Heiniö, Camilla, Zafar, Sadia, Garcia-Vallejo, Juan J., van Beusechem, Victor W., de Gruijl, Tanja D., Kalervo, Aino, Sorsa, Suvi, Kanerva, Anna, Hemminki, Akseli
Source:	Frontiers in immunology, 12:706517
Publication Year:	2021
Collection:	Publisso (ZB MED-Publikationsportal Lebenswissenschaften)
Subject Terms:	Female [MeSH], Immunology, Mice, Inbred C57BL [MeSH], Adenoviridae [MeSH], Oncolytic Virotherapy/methods [MeSH], Animals [MeSH], checkpoint inhibitor resistance, Programmed Cell Death 1 Receptor/antagonists, Tumor Necrosis Factor-alpha/immunology [MeSH], cancer immunotherapy, Mice [MeSH], Interleukin-2/immunology [MeSH], Melanoma, Experimental/pathology [MeSH], oncolytic virus, tumor microenvironment, adenovirus, Drug Resistance, Neoplasm [MeSH], Immune Checkpoint Inhibitors/pharmacology [MeSH]
Description:	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.
Document Type:	article in journal/newspaper
Language:	unknown
Relation:	https://repository.publisso.de/resource/frl:6478503; https://doi.org/10.3389/fimmu.2021.706517; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343222/
DOI:	10.3389/fimmu.2021.706517
Availability:	https://repository.publisso.de/resource/frl:6478503 https://doi.org/10.3389/fimmu.2021.706517 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343222/
Rights:	https://creativecommons.org/licenses/by/4.0/
Accession Number:	edsbas.5397824F
Database:	BASE

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