MUC1 antigen conjugated to inhibitor bulk reduced Idelalisib CLL mannan results in class II presentation and a T2 immune response [8]. Both conjugate formulations, oxidized and reduced mannan, bind equally to the MR and are taken up into early endosomes [8]. MUC1-oxidized mannan rapidly escapes from the early endosomes into the cytosol for proteasomal processing

and transport to the endoplasmic Inhibitors,research,lifescience,medical reticulum, Golgi apparatus, and MHC class I on the cell surface. By contrast, MUC1-reduced mannan remains in the early endosomes, to late endosomes, and to lysosomes, resulting in MHC class II presentation of antigens. Furthermore, both oxidized and reduced mannan stimulated bone marrow derived DCs, showed enhanced allogeneic

T-cell proliferation, and enhanced OTI/OTII peptide specific T-cell responses in vitro. Mice injected with oxidized or reduced mannan induced a mature phenotype of lymph node and splenic DCs [11]. Oxidized and reduced mannan both stimulated upregulation of inflammatory cytokines interleukin-(IL-) 1beta and tumour necrosis Inhibitors,research,lifescience,medical factor-alpha; Inhibitors,research,lifescience,medical however, oxidized mannan stimulated IFN-gamma, IL-12p40 cytokines whereas reduced mannan stimulated IL-4, IL-10, and IL-13 [11]. Moreover, the activation of DCs was toll-like receptor-4 (TLR-4) dependent [11]. Thus, the mode of mannan conjugation to antigen is important as the differential immune responses result [12–18]. These studies provided the first demonstration that Inhibitors,research,lifescience,medical the MR aided antigens into both the MHC class I or II pathways depending on the chemical modification of mannan. In addition, ex vivo targeting of macrophages

or DCs with oxidized mannan-MUC1 and reinjection into mice, induces strong CTL responses and protects against MUC1 tumor challenge [6, 19–21]. Humans are injected with oxidized mannan-MUC1 which induce Inhibitors,research,lifescience,medical cellular and humoral immune responses and protect against recurrence in breast cancer patients [21–24]. Ex vivo culture of human DC and pulsing with oxidized mannan-MUC1 and reinjection into patients with adenocarcinoma result in strong cellular immune responses and clinical responses [25]. Moreover, reduced mannan conjugated to myelin basic protein (MBP) 87–99 or 83–99 altered peptide ligands [26–28] (R91A96MBP87-99, A91A96MBP87-99, and Y91MBP83-99) divert Th1 IFN-gamma responses to Th2 IL-4 responses [29, 30]. Likewise, reduced mannan conjugated to cyclic A91A96MBP87-99 GSK-3 and A91MBP83-99 peptides significantly altered predominant Th1 responses to predominant Th2 responses [31–33]. Thus, mannan in its oxidized form has been shown to be effective as an anticancer vaccine, and mannan in its reduced form shows promise as a vaccine against autoimmune diseases such as multiple sclerosis. DNA immunization is an attractive form of vaccination, which has shown promising results only in small animal models.