In addition, modified liposome-LexLeB encapsulating the melanoma antigen MART-1 in the presence of lipopolysaccharide also enhanced CD8+ T-cell clone activation in vitro [93].

Polyamidoamine dendrimers comprising LeB antigen are taken into lysosomes, and dendrimers containing at least 16–32 glycan units are necessary for antigen presentation and cytokine production [94]. Thus, complexes using Le oligosaccharides to target DC-SIGN represent a novel method for vaccination against tumor antigens. Likewise, lentivirus AMN-107 manufacturer vectors modified with Sindbis virus envelope proteins, when linked to OVA, are taken up by murine bone marrow derived DCs and stimulate OT-I and OT-II Inhibitors,research,lifescience,medical T cells, CTL in vivo and protects mice against the challenge of OVA expressing tumor cells [95]. The binding of the modified lentivirus vectors Inhibitors,research,lifescience,medical with Sindbis virus envelope proteins to DC-SIGN is mannose dependent. Further modification of the vector to include 1-deoxymannojirimycin and to inhibit mannosidases (an enzyme that removes mannose structures during glycosylation) resulted in enhanced antibody responses [96]. These studies demonstrate that glycoconjugates could be Inhibitors,research,lifescience,medical designed

to target DC-SIGN for developing tumor vaccines. The use of glycans to target DC-SIGN has advantages over anti-DC-SIGN monoclonal antibodies, as they reduce the risk of side effects and their generation relies purely in organic chemistry approaches. However, a recent study demonstrated that receptor-specific antibodies are more effective at inducing Inhibitors,research,lifescience,medical immune responses than carbohydrates (glycans) for DC-targeted vaccination strategies [97]. L-SIGN or DC-SIGNR. L-SIGN or DC-SIGNR (also known as CD299, CD209L, and Clec4M) is a type-II transmembrane C-type lectin receptor homologous to DC-SIGN (77% amino acid sequence homology), highly expressed on liver sinusoidal cells, endothelial Inhibitors,research,lifescience,medical vascular cells, and in the lymph nodes, but not on DCs, in contrast to

DC-SIGN (Table 1 and Figure 1). Like DC-SIGN, L-SIGN has a high affinity binding to ICAM-3, HIV, simian immunodeficiency virus, Ebola virus, hepatitis C virus and respiratory syncytial virus [72, 73, 75]. L-SIGN also binds with HIV gp120-binding protein and Man9GlcNAc2 oligosaccharide, and however binding is enhanced up to 25-fold with Man9GlcNAc2 di-saccharide [98]. Antibodies against L-SIGN, are taken up by human liver sinusoidal endothelial cells and a cross-reactive antibody to L-SIGN/DC-SIGN conjugated to tetanus toxoid induced T-cell responses against tetanus toxoid. Thus, targeting L-SIGN shows promise for the development of targeted vaccines [99]. A further 8-mouse homologs to human DC-SIGN have been documented: SIGN-related gene 1 (SIGN-R1), SIGN-R2, SIGN-R3, SIGN-R4, SIGN-R5, SIGN-R6, SIGN-R7, SIGN-R8 [100].