NOUVELLE APPROCHE POUR L'IMMUNOTHÉRAPIE ANTI-TUMORALE : SYNTHÈSE ET ÉVALUATION DE GLYCOPROTÉINES MODULAIRES BRANCHÉES ANALOGUES DE MUC1 OBTENUES PAR LIGATION CHIMIQUE.

Abstract : The aim of the work presented in this thesis was the development of a robust method for the synthesis of small glycosylated modular proteins in order to develop original glycoprotein analogues of MUC1 able to induce an immune response against tumor-associated forms of MUC1.
First, the synthesis of a small triple-branched modular protein consisting of two repeat units of MUC1 and a PADRE epitope was developed using oxime ligation. The immunogenicity of the construct was tested in mice. The results show a marked influence of the branched geometry and of the presence of the T-helper epitope on the immunogenicity of the proteins.
Second, the same methodology was applied to the assembly of glycosylated chimeric proteins leading to the first synthesis of modular glycoprotein analogues of MUC1 linked by oxime bonds and carrying the saccharidic epitopes Tn (GalNAc) and T (GalGalNAc). The immunogenicity of these compounds was tested which allowed to compare the influence of the glycosylation on the immunogenicity of our constructions. This work opens the way to many studies which will enrich our knowledge on the role of glycans in the function of small glycoproteins as well as on the influence of sugars on the immune response to tumor antigens like MUC1.
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Gaëlle-Anne Cremer. NOUVELLE APPROCHE POUR L'IMMUNOTHÉRAPIE ANTI-TUMORALE : SYNTHÈSE ET ÉVALUATION DE GLYCOPROTÉINES MODULAIRES BRANCHÉES ANALOGUES DE MUC1 OBTENUES PAR LIGATION CHIMIQUE.. domain_other. Université d'Orléans, 2005. Français. ⟨tel-00011396⟩

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