Polyanhydride nanoparticle vaccine platform delays tumor growth

JOURNAL OF IMMUNOLOGY(2013)

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摘要
Abstract Immunotherapies designed to direct the immune system to elimate malignancies is a growing area of research aimed at providing a safe and effective alternative and/or adjunct therapy to chemotherapeutic and surgical interventions. These approaches require the development of immunization regimens that induce efficacious cell-mediated immunity directed at antigens expressed by tumor cells. Particles consisting of polyanhydride copolymers based on 1,6-bis(p-carboxyphenoxy) hexane (CPH), and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctante (CPTEG) have been shown to enhance dendritic cell activation, which in turn induces activation and proliferation of antigen-specific CD4+ and CD8+ T cells in vitro. We demonstrate that immunization of mice with a polyanhydride nanoparticle-based vaccine platform induced a potent immune response to a specific tumor-associated model antigen in order to control tumor progression in vivo. Specifically, we challenge immunized mice with a transgenic tumor cell line, expressing ovalbumin (Ova) as a target antigen, to determine if our vaccination strategy is effective. Mice immunized once with a regimen consisting of soluble Ova and Ova encapsulated in 20:80 CPTEG:CPH nanoparticles exhibited delayed tumor growth during the course of our study when compared to mice immunized with soluble Ova adjuvanted with Alum, soluble Ova alone, or PBS. Mice that receive the nanoparticle formulation also have improved survival rates when compared other formulations.
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