ArticleJournal of nanobiotechnology2026
A novel mRNA-based multi-cytokine strategy to reprogram the peritoneal tumor microenvironment in ovarian cancer.
Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPeritoneal dissemination is a hallmark feature of advanced ovarian cancer and significantly contributes to its poor prognosis. An intraperitoneal mRNA-based immunotherapy delivering a combination of single-chain interleukins (IL), including IL-12, IL-15, pro-IL-18, and Caspase-1, encapsulated in lipid nanoparticles, is administered to reprogram the immunosuppressive tumor microenvironment (TME) in a syngeneic ID8-Fluc ovarian cancer mouse model.
resultsThis mRNA cocktail effectively suppresses tumor growth, reduces malignant ascites, and inhibits metastasis. Immune profiling reveals enhanced infiltration of effector CD8⁺ and CD4⁺ T cells, reduced regulatory T cells, and decreased expression of exhaustion markers such as TIM-3 and PD-1. Macrophage populations are shifted from immunosuppressive M2 to proinflammatory M1 phenotypes, with increased monocyte infiltration, indicating robust myeloid reprogramming. Although mRNA-expressed IL-12 monotherapy exhibits potent antitumor effects, the combination of IL-15, IL-18, and Caspase-1 elicits superior therapeutic efficacy. Although high-dose treatment induces hepatotoxicity and weight loss, a reduced-dose regimen maintains efficacy with improved safety.
conclusionsThis study demonstrates the therapeutic potential of mRNA-based cytokine combinations to transform the ovarian cancer immune landscape. The modularity, localized delivery, and tunable expression of this platform provide a compelling framework for future mRNA immunotherapies targeting solid tumors with immunosuppressive TMEs.
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