Robust immune responses elicited by a fully synthetic three-component vaccine.
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 co-stimulatory proteins, enhanced uptake by macrophages and dendritic cells and avoidance of epitope suppression.
Ingale
Sampat
S
Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, USA.
Wolfert
Margreet A
MA
Gaekwad
Jidnyasa
J
Buskas
Therese
T
Boons
Geert-Jan
GJ
D000595:Amino Acid Sequence; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000276:immunology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D006020:Glycopeptides / Q000138:chemical synthesis / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D016207:Cytokines; D000939:Epitopes; D006020:Glycopeptides; D007074:Immunoglobulin G; D010446:Peptide Fragments; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2