{"entity": "publication", "iuid": "e99479c6424d4563a31d4792d89a001c", "timestamp": "2026-08-22T06:55:32.849Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e99479c6424d4563a31d4792d89a001c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e99479c6424d4563a31d4792d89a001c"}}, "title": "Immune priming using DC- and T cell-targeting gene therapy sensitizes both treated and distant B16 tumors to checkpoint inhibition.", "authors": [{"family": "Wenthe", "given": "Jessica", "initials": "J"}, {"family": "Naseri", "given": "Sedigheh", "initials": "S"}, {"family": "Hellstr\u00f6m", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Moreno", "given": "Rafael", "initials": "R"}, {"family": "Ullenhag", "given": "Gustav", "initials": "G"}, {"family": "Alemany", "given": "Ramon", "initials": "R"}, {"family": "L\u00f6vgren", "given": "Tanja", "initials": "T"}, {"family": "Eriksson", "given": "Emma", "initials": "E"}, {"family": "Loskog", "given": "Angelica", "initials": "A"}], "type": "journal article", "published": "2022-03-17", "journal": {"title": "Mol Ther Oncolytics", "issn": "2372-7705", "volume": "24", "pages": "429-442", "issn-l": "2372-7705"}, "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 immunocompetent 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 \u03b3 (IFN-\u03b3), tumor necrosis factor alpha (TNF-\u03b1), 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.", "doi": "10.1016/j.omto.2022.01.003", "pmid": "35141399", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8810301"}, {"db": "pii", "key": "S2372-7705(22)00007-9"}], "notes": [], "created": "2026-08-21T11:27:05.626Z", "modified": "2026-08-21T11:27:05.638Z"}