“Application of pH-sensitive fusogenic polymer-modified liposomes for development of cancer vaccines”
Activation of immune systems for cancer therapy has received much attention. Dendritic cells (DCs), potent professional antigen-presenting cells, play an important role in activation of innate and adaptive immunity. Therefore, we have developed pH-sensitive liposomes, which generate fusion ability under weakly acidic conditions, by surface modification of liposomes with pH-sensitive fusogenic polymer having carboxyl groups, such as succinylated poly(glycidol) (SucPG) for efficient delivery of cancer-specific antigens into DCs. In this study, the usefulness of pH-sensitive fusogenic polymer (SucPG)-modified liposomes (SucPG-liposomes) as cancer vaccine in the induction of antitumor immune responses was evaluated. Subcutaneous administration of SucPG-modified liposomes loaded with OVA (group I) induced generation of OVA-specific cytotoxic T cells (CTL) much more effectively than OVA alone. Furthermore, mice were subcutaneously immunized with OVA-containing adjuvant (monophosphoryl lipid A (MPL) (group II) or α-galactosylceramide (α-Gal))-modified SucPG-liposomes (group III). After immunization, significant antigen-specific antibodies were detected in the serum from groups I, II and III. Substantial production of IFN-γ (Th1-type) and IL-4 (Th2-type) was also demonstrated in spleen cells from mice of groups I, II and III in vitro. Especially, production of IFN-γ and IL-4 was higher in mice of group III than in groups I and II. Moreover, administration of the OVA-loaded SucPG-liposomes and α-Gal-modified OVA-loaded SucPG-liposomes to mice resulted in the growth inhibition of E.G7-OVA tumor, although the OVA alone didn’t affect tumor growth. These results suggest that the SucPG-liposomes, especially α-Gal-modified SucPG-liposomes, would serve effectively as cancer vaccine for efficient cancer immunotherapy.