![]() α-GalCer can therefore be used not only as a potential therapy for autoimmune diseases, infectious diseases, and cancer ( 11, 12), but also as an adjuvant to enhance the efficacy of various vaccines ( 13). After recognition, α-GalCer activates iNKT cells to rapidly produce large quantities of Th1 and Th2 cytokines ( 2), and subsequently induces a cascade of activation of various immune competent cells, including dendritic cells (DC) ( 3, 4), natural killer (NK) cells ( 5, 6), B cells ( 7, 8), and CD4 + and CD8 + T cells ( 9, 10). This α-GalCer is presented by CD1d, a MHC class I–like molecule, which is then recognized by the invariant t cell receptor ( invTCR) of iNKT cells. Through this rigorous and iterative screening process, we have identified a lead candidate glycolipid, 7DW8-5, that exhibits a superior adjuvant effect than α-GalCer on HIV and malaria vaccines in mice.Īlpha-Galactosylceramide (α-GalCer), a glycolpid composed of α-linked sugar and lipid moieties, is a well known specific lipid antigen for invariant natural killer T ( iNKT) cells ( 1). Assays included quantification of the magnitude of stimulatory activity against human iNKT cells in vitro, binding affinity to human and murine CD1d molecules, and binding affinity to the invariant t cell receptor of human iNKT cells. In our search for a glycolipid that can exert more potent stimulatory activity against iNKT cells and dendritic cells and produce an adjuvant effect superior to α-GalCer, we performed step-wise screening assays on a focused library of 25 α-GalCer analogues. However, in phase I clinical trials, α-GalCer was shown to display only marginal biological activity. The glycolipid α-galactosylceramide (α-GalCer) has been shown to bind CD1d molecules to activate invariant natural killer T ( iNKT) cells, and subsequently induce activation of various immune-competent cells, including dendritic cells, thereby providing a significant adjuvant effect for various vaccines.
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