Alpha-galactosylceramide (α-GalCer) is a glycolipid that can be loaded into MHC-class-I-related CD1d molecules by dendritic cells and has been shown to stimulate invariant natural killer T (iNKT) cells. iNKT cells have emerged as important contributors to the regulation of immune responses, T cell activation, and anti-tumor activity. Through this activation cascade, α-GalCer exerts potent anti-tumoral and immune regulatory activities. However, the limitations were found in clinical application that (1) iNKT cells failed to produce cytokines and proliferate when additional doses of α-GalCer were given by systemic route and (2) poor hydrophilicity of α-GalCer. In this project, α-GalCer was incorporated into the lipid bilayer of the liposome, while the galactose molecular was expressed on the surface of the liposome to form a targeting liposome antigen-carrier with immunemodulatory effect. Thus, α-GalCer-incorporated liposome is capable of improving the delivery of antigen to antigen-presenting-cell and inducing effective immune responses via various routes. In this project, we will investigate preparation of α-GalCer-incorporated liposomes, in vitro and in vivo mechanisms, and the application in cancer vaccine therapy of α-GalCer-incorporated liposomes. During the first year, we will prepare α-GalCer-incorporated liposomes and the characteristics of α-GalCer-incorporated liposomes will be analyzed. The maturation and cytokine production of dendritic cells will also be investigated after cultured with α-GalCer-incorporated liposomes in vitro. During the second year, mice will be immunized with α-GalCer-incorporated liposome vaccine via intravenous or intranasal routes and T cell activities will be analyzed. Cytokines, antigen-specific antibodies and subtype antibodies of serum and nasal wash fluid will be analyzed in order to investigate the enhancement of the Th1/Th2 immune-modulatory pathway. For the last year, mice will be immunized and the activities of cytotoxic T cells and NK cells will be illustrated. Furthermore, the therapeutic efficacy of α-GalCer-incorporated liposome against tumor will be investigated.
|Effective start/end date||8/1/15 → 7/31/16|
- targeting liposome carrier
- dendritic cell
- invariant natural killer T cell
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