Journal of Vaccine Research 2024, Vol.14, No.4, 183-195 http://medscipublisher.com/index.php/jvr 186 effective for cancer vaccines. TLR agonists such as polyinosinic-polycytidylic acid (polyICLC) and monophosphoryl lipid A (MPL) have been shown to induce strong anti-tumor immune responses (Seya et al., 2015; Melssen et al., 2019; Luchner et al., 2021; Yang et al., 2022; Heo et al., 2023; Jeon et al., 2024). They work by activating dendritic cells and promoting the cross-presentation of tumor antigens, which is crucial for the activation of cytotoxic T lymphocytes (CTLs) (Lee and Suresh, 2022). 3.4 Saponin-based adjuvants Saponin-based adjuvants, such as QS-21, are derived from natural sources and have been shown to enhance both humoral and cellular immune responses. These adjuvants are particularly effective in promoting the cross-presentation of antigens by dendritic cells, leading to robust CTL responses (Figure 2) (den Brok et al., 2012; Lee and Suresh, 2022). When combined with in situ tumor destruction methods, saponin-based adjuvants have demonstrated unprecedented levels of anti-tumor immunity, making them highly effective for cancer vaccines (Brok et al., 2012). Figure 2 Mechanisms of Adjuvant-mediated Cross-presentation in DCs (Adopted from Lee and Suresh, 2022) Image caption: I. Alum-based nanoparticles: Antigens that are coupled with Alum-based nanoparticles are taken up by scavenger receptor A. Antigens are translocated from phagosomes-to-cytosol, further processed by cytosolic proteasomes, and loaded onto MHC-I molecules by TAP-dependent mechanism. II. Saponin-based adjuvants: Saponin-based adjuvants induce the formation of intracellular lipid bodies (LB). Internalized antigens are localized in the phagosomes, which are released into cytosol facilitated by lysosomal proteases, and degraded by cytosolic proteasomes. The digested peptides are translocated back to ER by TAP transporters and loaded onto MHC I molecules. III. TLR-based adjuvants: Ligation of TLR agonist induces phagocytosis of antigen mediated by Myd88-IKK2-SNAP23 and recruitment of endosomal recycling complex, marked by Rab11a and VAMP 3/8. TLR-based adjuvants also elicit the formation of perinuclear clustering of lysosomes, which leads to delayed fusion of phagolysosomes. IV. Carbomer-based adjuvants: Carbomer-based adjuvants induce the formation of intracellular lipid bodies. Carbomer-based adjuvants also induce the production of ROS in the phagosomes. The internalized antigens escape from phagosomes to cytosol, which are subsequently processed by cytosolic proteasomes, translocated using TAP transporters, and loaded onto MHC-I molecules (Adopted from Lee and Suresh, 2022)
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