title: Incorporation of polyinosine-polycytidylic acid enhances cytotoxic T cell activity and antitumor effects by octaarginine-modified liposomes encapsulating antigen, but not by octaarginine-modified antigen complex.
abstract: In a previous study, we reported on the efficient delivery of an antigen to the cytosol and a specific-antigen presentation on MHC class I in dendritic cells by rationally controlling the intracellular trafficking of ovalbumin (OVA), a model antigen, with stearylated octaarginine-modified liposomes (R8-Lip/OVA). However, no significant difference in antitumor effects against E.G7-OVA, OVA expressed lymphoma, was observed between R8-Lip/OVA and an electrostatic complex of R8 and OVA (R8/OVA-Com). In this study, we hypothesized that use of adjuvants clarified the difference in immune responses between R8-Lip/OVA and R8/OVA-Com, and selected polyinosine-polycytidylic acid (polyI:C) as an adjuvant. Cytotoxic T lymphocyte (CTL) activity of the polyI:C and OVA encapsulated R8-Lip (R8-Lip/PIC/OVA) was drastically enhanced compared to R8-Lip/OVA and complete Freund's adjuvant with OVA. Moreover, the incorporation of polyI:C clearly was critical for the difference in antitumor effects and CTL activities between R8-Lip/OVA and R8/OVA-Com. These findings suggest that the carriers that are incorporated polyI:C has a great influence on the induction of cellular immunity in vivo.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Rumiko
authors.initials: R
authors.lastname: Moriguchi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kogure
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D007111:Immunity, Cellular / Q000276:immunology; D008081:Liposomes; D008223:Lymphoma / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D011070:Poly I-C / Q000008:administration & dosage* / Q000494:pharmacology; D055672:Static Electricity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D008081:Liposomes; D009842:Oligopeptides; C448619:octaarginine; D010047:Ovalbumin; D005620:Freund's Adjuvant; D011070:Poly I-C