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J Control Release. 2011 Jun 10;152(2):310-6. doi: 10.1016/j.jconrel.2011.03.009. Epub 2011 Mar 22.

Intranasal immunization with poly(γ-glutamic acid) nanoparticles entrapping antigenic proteins can induce potent tumor immunity.

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Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.


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.

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