title: Intranasal immunization with poly(γ-glutamic acid) nanoparticles entrapping antigenic proteins can induce potent tumor immunity.
abstract: We previously reported strong induction of ovalbumin (OVA)-specific tumor immunity in mice injected subcutaneously with OVA-entrapping nanoparticles comprising amphiphilic poly(γ-glutamic acid) (OVA/γ-PGA NPs). In the present study we investigated antitumor efficacy and associated immune responses in mice vaccinated with OVA/γ-PGA NPs via the nasal cavity. Mice vaccinated intranasally with OVA/γ-PGA NPs resisted challenge by E.G7-OVA tumor cells, and lung metastasis of B16-OVA cells were significantly suppressed by three intranasal doses of OVA/γ-PGA NPs. Although the total serum anti-OVA IgG titer was equivalent between the OVA/γ-PGA NP- and OVA solution-immunized groups, intranasal vaccination with OVA/γ-PGA NPs efficiently induced cytotoxic T lymphocytes (CTLs) and interferon-γ-secreting cells specific for OVA in the spleen and lymph nodes. The antitumor activity induced by intranasal vaccination of OVA/γ-PGA NPs mainly required CD8(+) CTLs, and the development of long-term specific immunity was confirmed in rechallenge experiments. OVA/γ-PGA NPs administered via the nasal cavity were rapidly taken up by nasopharyngeal-associated lymphoid tissue and delivered to the cervical lymph nodes. Thus, nasal vaccination with antigen-entrapping γ-PGA NPs evokes tumor immunity by eliciting antigen-specific CTLs. γ-PGA NPs are a promising antigen delivery carrier for the development of non-invasive cancer vaccines.
authors.affiliation: Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsuo
authors.forename: Hayato
authors.initials: H
authors.lastname: Koizumi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Fujita
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Okada
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control*; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D019496:Cancer Vaccines; D004337:Drug Carriers; D007074:Immunoglobulin G; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D010047:Ovalbumin