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Interleukin-12 (IL-12) displayed on Tumor Membrane Vesicles (TMVs) is an engineered cancer vaccine platform designed to deliver the potent pro-inflammatory cytokine IL-12 directly to the tumor microenvironment or vaccination site [26, 27]. IL-12 is a heterodimeric cytokine (p35 and p40 subunits) that plays a critical role in bridging innate and adaptive immunity by promoting the differentiation of naive T cells into Th1 cells and stimulating the production of interferon-gamma (IFN-γ) from T cells and natural killer (NK) cells [10, 15]. While systemic administration of recombinant IL-12 has been limited by severe toxicity, displaying IL-12 on the surface of TMVs—often via a glycosylphosphatidylinositol (GPI) anchor—allows for localized immune activation and reduced systemic exposure [26, 33]. This approach leverages the natural tumor-associated antigens present on the TMVs to prime a specific anti-tumor response while the anchored IL-12 acts as a powerful adjuvant to overcome the immunosuppressive tumor microenvironment [29, 33]. Preclinical studies have demonstrated that IL-12-modified TMVs can induce robust T cell proliferation, enhance cytotoxic activity, and promote tumor regression in various models, including melanoma and breast cancer [27, 29].
Localized delivery and display of Interleukin-12 on tumor-derived vesicles to activate the IL-12 receptor signaling pathway (JAK-STAT) in T cells and NK cells, thereby promoting a Th1-polarized anti-tumor immune response and overcoming the immunosuppressive tumor microenvironment.
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