'Multicopy multivalent' glycopolymer-stabilized gold nanoparticles as potential synthetic cancer vaccines.

Journal article

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: Parry, A; Clemson, N; Ellis, J; Bernhard, S; Davis, B

• Publication status: Published
• Peer review status: Peer reviewed
• Journal: Journal of the American Chemical Society
• Volume: 135
• Issue: 25
• Pages: 9362-9365
• Publication date: 2013-06-17
• DOI: 10.1021/ja4046857
• EISSN: 1520-5126
• ISSN: 0002-7863
• Language: English
• Keywords: Antigens, Tumor-Associated, Carbohydrate; Cancer Vaccines; Molecular Structure; Polymers; Polymerization; Metal Nanoparticles; Gold