Letter abstract
Nature Chemical Biology 3, 663 - 667 (2007)
Published online: 2 September 2007 | doi:10.1038/nchembio.2007.25
Robust immune responses elicited by a fully synthetic three-component vaccine
Sampat Ingale1, Margreet A Wolfert1, Jidnyasa Gaekwad1, Therese Buskas1 & Geert-Jan Boons1
The overexpression of saccharides such as Globo-H, LewisY 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 co-stimulatory proteins, enhanced uptake by macrophages and dendritic cells and avoidance of epitope suppression.
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, USA.
Correspondence to: Geert-Jan Boons1 e-mail: gjboons@ccrc.uga.edu
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