ReviewFrontiers in immunology2026
Cytokine delivery and targeting strategies in pet dogs with cancer: a comparative immuno-oncology approach.
Review in Frontiers in immunology, 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
Cytokine therapies have long been hampered by a fundamental pharmacological problem: systemic absorption and distribution drives immune-related toxicity which precludes the achievement of therapeutic concentrations within tumors to mediate anti-tumor immunity. Engineering cytokines with tunable biodistribution properties to remain within or near the injection site has reinvigorated opportunities to explore cytokine-based immunotherapies for clinical evaluation. Pet dogs with spontaneous cancers offer a biologically rich and informative model system for investigating new therapeutic delivery strategies. Pet dogs develop tumors naturally in an immunocompetent setting, share key features of human tumor immunobiology and immune system architecture, and display similar pharmacodynamic immune biomarkers used for assessing tolerability and antitumor activities in human cancer patients. This mini review examines targeted cytokine delivery platforms evaluated in pet dogs with naturally occurring malignancies, including aluminum hydroxide-anchored IL-12, collagen-binding IL-2/IL-12 fusion proteins, antibody-cytokine immunocytokines (NHS-IL12 and hu14.18-IL2), PEGylated TNF-α, liposomal IL-2, plasmid IL-12 electrogene therapy, oncolytic viruses engineered to express IL-12 or IFN-β, and emerging delivery platforms. Solid malignancies studied in pet dogs include melanoma, soft tissue sarcoma, mast cell tumor, osteosarcoma, high-grade glioma, adenocarcinoma, fibrosarcoma, and urothelial carcinoma. Across diverse technological platforms, several pharmacodynamic patterns observed in dogs have also been recapitulated in first-in-human trials, emphasizing the potential wealth of a comparative oncology framework for evaluating novel immunomodulatory strategies. These parallels underscore the value of canine immuno-oncology trials in defining safety and biological activity for engineered cytokine constructs, with direct implications for guiding the development of dose selection and biomarker discovery in the human immuno-oncology field.
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