title: 'Multicopy multivalent' glycopolymer-stabilized gold nanoparticles as potential synthetic cancer vaccines.
abstract: Mucin-related carbohydrates are overexpressed on the surface of cancer cells, providing a disease-specific target for cancer immunotherapy. Here, we describe the design and construction of peptide-free multivalent glycosylated nanoscale constructs as potential synthetic cancer vaccines that generate significant titers of antibodies selective for aberrant mucin glycans. A polymerizable version of the Tn-antigen glycan was prepared and converted into well-defined glycopolymers by Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization. The polymers were then conjugated to gold nanoparticles, yielding 'multicopy-multivalent' nanoscale glycoconjugates. Immunological studies indicated that these nanomaterials generated strong and long-lasting production of antibodies that are selective to the Tn-antigen glycan and cross-reactive toward mucin proteins displaying Tn. The results demonstrate proof-of-concept of a simple and modular approach toward synthetic anticancer vaccines based on multivalent glycosylated nanomaterials without the need for a typical vaccine protein component.
authors.affiliation: Department of Chemistry and Biophysical Sciences Institute, Durham University , South Road, Durham, DH1 3LE, UK.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Parry
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Clemson
authors.forename: James
authors.initials: J
authors.lastname: Ellis
authors.forename: Stefan S R
authors.initials: SS
authors.lastname: Bernhard
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Davis
authors.forename: Neil R
authors.initials: NR
authors.lastname: Cameron
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry; D019496:Cancer Vaccines / Q000138:chemical synthesis* / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D015394:Molecular Structure; D058105:Polymerization; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D011108:Polymers; D006046:Gold