ArticleJournal of experimental & clinical cancer research : CR2025
Antibody-based delivery of interleukin-2 modulates the immunosuppressive tumor microenvironment and achieves cure in pancreatic ductal adenocarcinoma syngeneic mice.
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Cytokine fusion proteins for solid tumor therapy: mechanistic insights and clinical advances.Journal of hematology & oncology · 2026Review
- Imaging-guided optimization of biodistribution and antitumor efficacy of L19-based immunocytokines.Translational oncology · 2026Article
- Tumor-targeted IL2 promotes specific CD8Journal of experimental & clinical cancer research : CR · 2026Article
- Targeting IL-12 for pancreatic cancer immunotherapy: advances in delivery strategies and clinical translation.Frontiers in immunology · 2026Review
- Transcriptional and Epigenetic Plasticity Drive an Alternative Non-clonal Mechanism of Resistance toCancer communications (London, England) · 2026Article
- Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Cancer therapy resistance from a spatial-omics perspective.Clinical and translational medicine · 2025Review
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15 authors.
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Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadly type of cancer, with an extremely low five-year overall survival rate. To date, current treatment options primarily involve various chemotherapies, which often prove ineffective and are associated with substantial toxicity. Furthermore, immunotherapies utilizing checkpoint inhibitors have shown limited efficacy in this context, highlighting an urgent need for novel therapeutic strategies. This study investigates the preclinical efficacy of an innovative targeted therapy based on antibody-cytokine fusion proteins, specifically interleukin-2 (IL-2), a pivotal driver of cell-mediated immunity, fused to L19 antibody, which selectively binds to extra domain B of fibronectin (EDB-FN1) expressed in the tumor microenvironment.
methodsWe tested the effectiveness of different immunocytokines through in vivo characterization in syngeneic C57BL/6J orthotopic mouse models of PDAC. Based on these results, we decided to focus on L19-IL2. To assess the efficacy of this immunocytokine we developed an ex-vivo immune-spheroid interaction platform derived from murine 3D pancreatic cultures, and telomerase reverse transcriptase (TERT) specific T-lymphocytes. Moreover, we evaluated the anti-cancer effect of L19-IL2 in combination with standard therapy in vivo experiments in PDAC mouse models. Tumor samples collected after the treatments were characterized for tumor infiltrating immune cell components by bulk RNA sequencing (RNA-seq) and spatial transcriptomics (Stereo-seq) analysis.
resultsThe tumor-targeted L19-IL2 fusion protein demonstrated potent, dose-dependent anti-tumor activity in mice with pancreatic tumors resistant to standard chemotherapy. Spatial Transcriptomics (ST) and RNA-seq analyses indicated that L19-IL2 treatment induced a significant influx of immune cells into the tumor microenvironment, with these cells expressing activation markers like granzymes, perforins, and the IL-2 receptors.
conclusionsOur results demonstrated that L19-IL2 enhances immune infiltration and cytotoxicity, remodeling the "cold" tumor microenvironment (TME) in PDAC. This innovative antibody-cytokine fusion protein improves therapeutic outcomes, paving the way for novel targeted treatment strategies in PDAC.
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