Journal
NATURE CHEMICAL BIOLOGY
Volume 3, Issue 10, Pages 663-667Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nchembio.2007.25
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Funding
- NCI NIH HHS [R01 CA088986, R01 CA088986-07, R01 CA88986] Funding Source: Medline
- NIGMS NIH HHS [R01 GM061761] Funding Source: Medline
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The overexpression of saccharides such as Globo- H, Lewis(Y) and Tn antigen is a common feature of oncogenic transformed cells. Endeavors to exploit this aberrant glycosylation for cancer vaccine development have been complicated by difficulties in eliciting high titers of IgG antibodies against classical conjugates of tumor- associated carbohydrates to carrier proteins. We have designed, chemically synthesized and immunologically evaluated a number of fully synthetic vaccine candidates to establish strategies to overcome the poor immunogenicity of tumor- associated carbohydrates and glycopeptides. We have found that a three- component vaccine composed of a TLR2 agonist, a promiscuous peptide T- helper epitope and a tumor- associated glycopeptide can elicit in mice exceptionally high titers of IgG antibodies that can recognize cancer cells expressing the tumor- associated carbohydrate. The superior properties of the vaccine candidate are attributed to the local production of cytokines, upregulation of costimulatory proteins, enhanced uptake by macrophages and dendritic cells and avoidance of epitope suppression.
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