Chemoselective assembly and immunological evaluation of multiepitopic glycoconjugates bearing clustered Tn antigen as synthetic anticancer vaccines.
In this paper we investigated the use of regioselectively addressable functionalized templates (RAFTs) as new scaffolds for the design of anticancer vaccine candidates. We report the synthesis of well-defined multiepitopic RAFT scaffolds and their immunological evaluation. These conjugates exhibit clustered Tn analogue as tumor-associated carbohydrate antigen (TACA, B-cell epitope) and the CD4+ helper T-cell peptide from the type 1 poliovirus. The saccharidic and peptidic epitopes were both synthesized separately and combined regioselectively to the RAFT core using a sequential oxime bond formation strategy. B- and T-antigenicity and immunogenicity of the vaccine candidates were investigated in vitro and in vivo. These studies clearly demonstrate that the saccharidic part of the conjugates is recognized by Tn-specific monoclonal antibodies. Moreover, the antibodies elicited by immunization of mice with our vaccine candidates recognize the native form of Tn epitope expressed on human tumor cells. Together with oxime ligation technique, these results suggest that the RAFT scaffold provides a promising and suitable tool for engineering potent synthetic anticancer vaccine.
Grigalevicius
Saulius
S
LEDSS UMR 5616 and ICMG-FR2607, Université Joseph Fourier, BP 53, 38041 Grenoble Cedex 9, France.
Chierici
Sabine
S
Renaudet
Olivier
O
Lo-Man
Richard
R
Dériaud
Edith
E
Leclerc
Claude
C
Dumy
Pascal
P
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D019921:Biotinylation; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006001:Glycoconjugates / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D015394:Molecular Structure; D013601:T-Lymphocytes / Q000276:immunology
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D000939:Epitopes; D006001:Glycoconjugates