Stable Gold-Nanoparticle-Based Vaccine for the Targeted Delivery of Tumor-Associated Glycopeptide Antigens



Kevin R. Trabbic1, Kristopher A. Kleski1, and Joseph J. Barchi Jr1


  1. Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland 21702, United States


We have developed a novel antigen delivery system based on polysaccharide-coated gold nanoparticles (AuNPs) targeted to antigen-presenting cells (APCs) expressing Dectin-1. AuNPs were synthesized de novo using yeast-derived β-1,3-glucans (B13G) as the reductant and passivating agent in a microwave-catalyzed procedure, yielding highly uniform and serum-stable particles. These were further functionalized with both a peptide and a specific glycosylated form from the tandem repeat sequence of mucin 4 (MUC4), a glycoprotein overexpressed in pancreatic tumors. The glycosylated sequence contained the Thomsen–Friedenreich disaccharide, a pan-carcinoma, tumor-associated carbohydrate antigen (TACA), which has been a traditional target for antitumor vaccine design. These motifs were prepared with a cathepsin B protease cleavage site (Gly-Phe-Leu-Gly), loaded on the B13G-coated particles, and these constructs were examined for Dectin-1 binding, APC processing, and presentation in a model in vitro system and for immune responses in mice. We showed that these particles elicit strong in vivo immune responses through the production of both high-titer antibodies and priming of antigen-recognizing T-cells. Further examination showed that a favorable antitumor balance of expressed cytokines was generated, with limited expression of immunosuppressive Il-10. This system is modular in that any range of antigens can be conjugated to our particles and efficiently delivered to APCs expressing Dectin-1.

CovalX Technology Used



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Categories : Publications, High-Mass MS