Galactosylated liposome as a dendritic cell-targeted mucosal vaccine for inducing protective anti-tumor immunity

Abstract

Mucosal surfaces contain specialized dendritic cells (DCs) that are able to recognize foreign pathogens and mount protective immunity. We previously demonstrated that intranasal administration of targeted galactosylated liposomes can elicit mucosal and systemic antibody responses. In the present study, we assessed whether galactosylated liposomes could act as an effective DC-targeted mucosal vaccine that would be capable of inducing systemic anti-tumor immunity as well as antibody responses. We show that targeted galactosylated liposomes effectively facilitated antigen uptake by DCs beyond that mediated by unmodified liposomes both in vitro and in vivo. Targeted galactosylated liposomes induced higher levels of pro-inflammatory cytokines than unmodified liposomes in vitro. C57BL/6 mice thrice immunized intranasally with ovalbumin (OVA)-encapsulated galactosylated liposomes produced high levels of OVA-specific IgG antibodies in their serum. Spleen cells from mice receiving galactosylated liposomes were restimulated with OVA and showed significantly augmented levels of IFN-γ, IL-4, IL-5 and IL-6. In addition, intranasal administration of OVA-encapsulated beta-galactosylated liposomes resulted in complete protection against EG7 tumor challenge in C57BL/6 mice. Taken together, these results indicate that nasal administration of a galactosylated liposome vaccine mediates the development of an effective immunity against tumors and might be useful for further clinical anti-tumoral applications.

Keywords: Antigen delivery; Cancer immunotherapy; Dendritic cell targeted; Galactosylated liposome; Mucosal vaccine.