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http://hdl.handle.net/2445/184816
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DC Field | Value | Language |
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dc.contributor.author | Wenthe, Jessica | - |
dc.contributor.author | Naseri, Sedigheh | - |
dc.contributor.author | Hellström, Ann Charlotte | - |
dc.contributor.author | Moreno Olié, Rafael | - |
dc.contributor.author | Ullenhag, Gustav | - |
dc.contributor.author | Alemany Bonastre, Ramon | - |
dc.contributor.author | Lövgren, Tanja | - |
dc.contributor.author | Eriksson, Emma | - |
dc.contributor.author | Loskog, Angelica | - |
dc.date.accessioned | 2022-04-07T10:56:29Z | - |
dc.date.available | 2022-04-07T10:56:29Z | - |
dc.date.issued | 2022-03-01 | - |
dc.identifier.issn | 2372-7705 | - |
dc.identifier.uri | http://hdl.handle.net/2445/184816 | - |
dc.description.abstract | Immune checkpoint inhibitors have revolutionized the treatment of metastatic melanoma, but most tumors show resistance. Resistance is connected to a non-T cell inflamed phenotype partially caused by a lack of functional dendritic cells (DCs) that are crucial for T cell priming. Herein, we investigated whether the adenoviral gene vehicle mLOAd703 carrying both DC- and T cell-activating genes can lead to inflammation in a B16-CD46 model and thereby overcome resistance to checkpoint inhibition therapy. B16-CD46 cells were injected subcutaneously in one or both flanks of immuno-competent C57BL/6J mice. mLOAd703 treatments were given intratumorally alone or in combination with intraperitoneal checkpoint inhibition therapy (anti-PD-1, anti-PD-L1, or anti-TIM-3). Tumor, lymph node, spleen, and serum samples were analyzed for the presence of immune cells and cytokines/chemokines. B16-CD46 tumors were non-inflamed and resistant to checkpoint blockade. In contrast, mLOAd703 treatment led to infiltration of the tumor by CD8(+) T cells, natural killer (NK) cells, and CD103(+) DCs, accompanied by a systemic increase of pro-inflammatory cytokines interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-27 (IL-27). This response was even more pronounced after combining the virus with checkpoint therapy, in particular with anti-PD-L1 and anti-TIM-3, leading to further reduced tumor growth in injected lesions. Moreover, anti-PD-L1 combination also facilitated abscopal responses in non-injected lesions. | - |
dc.format.extent | 14 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier BV | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1016/j.omto.2022.01.003 | - |
dc.relation.ispartof | Molecular Therapy - Oncolytics, 2022, vol. 24, p. 429-442 | - |
dc.relation.uri | https://doi.org/10.1016/j.omto.2022.01.003 | - |
dc.rights | cc by (c) Wenthe, Jessica et al, 2022 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Melanoma | - |
dc.subject.classification | Cèl·lules T | - |
dc.subject.other | Melanoma | - |
dc.subject.other | T cells | - |
dc.title | Immune priming using DC- and T cell-targeting gene therapy sensitizes both treated and distant B16 tumors to checkpoint inhibition | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2022-04-07T09:48:00Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 35141399 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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PIIS2372770522000079.pdf | 1.01 MB | Adobe PDF | View/Open |
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