20.500.12556/DiRROS-27567 Chemokine CCL5 overexpression combined with radiotherapy modulates Th1-mediated immune response and leads to significant tumor growth delay in mouse tumor models This study investigated the antitumor efficacy of chemokine CCL5 gene therapy using gene electrotransfer (GET) in combination with radiotherapy (RT) in solid murine tumors CT26 and 4T1. In vitro, CT26 and 4T1 tumor cells transfected with plasmid DNA (pDNA) encoding CCL5 induced migration of RAW264.7 macrophages. In vivo, CCL5 overexpression achieved via GET of pDNA encoding CCL5 led to increased splenocyte infiltration in dorsal window chamber models. When combined with RT, GET of pDNA encoding CCL5 shifted the tumor cytokine profile toward a proinflammatory state, with elevated Ifn-γ, Cxcl9, Cxcl10, and Il-12α. Although CD8 + and CD4 + T cells were reduced post-treatment, due to radiation-induced cell death, the combination of GET of pDNA encoding CCL5 and RT significantly delayed tumor growth in both models. In 4T1 tumors, this delay was also significant compared to the equivalent treatment with GET of control pDNA. These findings support GET of pDNA encoding CCL5 combined with RT as a strategy to enhance immune-mediated tumor control. chemokines gene electrotransfer gene therapy mouse radiotherapy cemokini elektroprenos genov gensko zdravljenje miši radioterapija true false true Elsevier Masson SAS Basel, Switzerland Angleški jezik Slovenski jezik by Authors Neznano 2026-02-13 11:30:58 2026-02-13 11:30:58 2026-02-14 04:04:01 0000-00-00 00:00:00 2026 0 0 str. 118887-1-118887-18 Vol. 194 Jan. 2026 0000-00-00 Zaloznikova Objavljeno apc 2025-07-02 2025-12-03 2026-01-06 602.6/.7 0753-3322 10.1016/j.biopha.2025.118887 264675843 RAZ_Bozic_Tim_2026.pdf RAZ_Bozic_Tim_2026.pdf 1 CCB16C8D34FEC24DF3E50FDB96F1CE3E f64b2d4ae9030aee5a3e2f3a74d27e6a6c3e6a14d7283edd32907fda86ef4aa5 d88e23e8-08c7-11f1-bcbc-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=40385 Onkološki inštitut Ljubljana 0 0 0