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Immune-stimulating complexes (ISCOMs) are self-assembled, cage-like nanoparticles about 40–60 nm composed of Quillaja saponins, cholesterol, and phospholipids, used primarily as vaccine adjuvants rather than therapeutic receptor or enzyme targets.[1][4] ISCOMs can be prepared with antigen incorporated (ISCOM) or without antigen (ISCOM matrix/ISCOMATRIX), the latter functioning as an adjuvant mixed with antigen post-manufacture; Matrix-M is a specific ISCOM-derived adjuvant used clinically.[1][2] These saponin-based adjuvants uniquely induce strong humoral and cell-mediated immunity, enhancing MHC class I and II responses, promoting Th1 cytokines (e.g., IL-2, IFN-γ) and supporting CD8+ T-cell responses via cross-presentation.[2][5] Formulating saponins into ISCOMs reduces the hemolytic toxicity associated with free saponins while maintaining adjuvanticity, improves antigen stability, and facilitates dendritic cell interactions and cross-presentation.[1][3] Mechanistic studies show ISCOM Matrix C promotes antigen cross-presentation particularly in human CD163+ CD14+ cDC2 subsets, highlighting subset-specific effects relevant to cancer vaccine design.[5] ISCOM technology has been used across infectious disease and oncology vaccine research, can support mucosal immunity, and offers practical advantages including dose-sparing and stability in cold storage.[1][2]
Saponin–cholesterol–phospholipid nanoparticles enhance antigen uptake and stability; Promote dendritic cell activation and antigen cross-presentation to CD8+ T cells; Induce Th1 and Th2 responses with cytokines including IFN-γ and IL-2; Reduce free-saponin hemolysis by incorporating saponins into particulate complexes
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