‘Multicopy Multivalent’ Glycopolymer-Stabilized Gold Nanoparticles as Potential Synthetic Cancer Vaccines

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...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2013-06, Vol.135 (25), p.9362-9365
Main Authors: Parry, Alison L, Clemson, Natasha A, Ellis, James, Bernhard, Stefan S. R, Davis, Benjamin G, Cameron, Neil R
Format: Article
Language:English
Subjects:
Antibodies
Antigens, Tumor-Associated, Carbohydrate - chemistry
Cancer
Cancer Vaccines - chemical synthesis
Cancer Vaccines - chemistry
Communication
Construction
Glycan
Gold - chemistry
Metal Nanoparticles - chemistry
Molecular Structure
Nanomaterials
Nanostructure
Polymerization
Polymers - chemical synthesis
Polymers - chemistry
Vaccines
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Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja4046857