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 c...

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Bibliographic Details
Published in:Bioconjugate chemistry 2005-09, Vol.16 (5), p.1149-1159
Main Authors: Grigalevicius, Saulius, Chierici, Sabine, Renaudet, Olivier, Lo-Man, Richard, Dériaud, Edith, Leclerc, Claude, Dumy, Pascal
Format: Article
Language:English
Subjects:
Animals
Antigens
Antigens, Tumor-Associated, Carbohydrate - chemistry
Antigens, Tumor-Associated, Carbohydrate - immunology
B-Lymphocytes - immunology
Biochemistry
Biotinylation
Cancer
Cancer Vaccines - chemistry
Cancer Vaccines - immunology
Chemical Sciences
Epitopes - chemistry
Epitopes - immunology
Glycoconjugates - chemistry
Glycoconjugates - immunology
Immunology
Mice
Molecular Structure
Organic chemistry
Peptides
Poliovirus
T-Lymphocytes - immunology
Vaccines
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Summary: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.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc050010v