Synthesis and Biological Evaluation of an Anticancer Vaccine Containing the C-Glycoside Analogue of the Tn Epitope

The C-saccharide analogue of the GalNAc (Tn epitope) has been covalently linked to the T cell epitope peptide 328-340OVA using a chemoselective convergent synthetic approach. In this way, a non-hydrolyzable synthetic vaccine was obtained composed by a B epitope conjugated to a T cell epitope. This c...

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Bibliographic Details
Published in:Bioconjugate chemistry 2001-05, Vol.12 (3), p.325-328
Main Authors: Peri, Francesco, Cipolla, Laura, Rescigno, Maria, La Ferla, Barbara, Nicotra, Francesco
Format: Article
Language:English
Subjects:
Animals
Antigens, Tumor-Associated, Carbohydrate - chemistry
Antigens, Tumor-Associated, Carbohydrate - immunology
Antigens, Tumor-Associated, Carbohydrate - metabolism
Cancer Vaccines - chemical synthesis
Cancer Vaccines - immunology
Cancer Vaccines - pharmacology
Cell Line
Cross-Linking Reagents
Dendritic Cells - drug effects
Dendritic Cells - immunology
Epitopes, B-Lymphocyte - chemistry
Epitopes, B-Lymphocyte - immunology
Epitopes, T-Lymphocyte - chemistry
Epitopes, T-Lymphocyte - immunology
Glycopeptides - chemical synthesis
Glycopeptides - immunology
Glycosides - chemistry
Histocompatibility Antigens Class II - immunology
Histocompatibility Antigens Class II - metabolism
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Mice
Mice, Transgenic
Monosaccharides - chemistry
Monosaccharides - immunology
Ovalbumin - immunology
Spleen - cytology
Spleen - drug effects
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
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Summary:The C-saccharide analogue of the GalNAc (Tn epitope) has been covalently linked to the T cell epitope peptide 328-340OVA using a chemoselective convergent synthetic approach. In this way, a non-hydrolyzable synthetic vaccine was obtained composed by a B epitope conjugated to a T cell epitope. This compound was tested in a proliferation assay with spleen cells from DO11.10 mice. The molecule was recognized by transgenic T cells although at a slightly lower efficiency if compared with the reference peptide OVA. An additional experiment with dendritic cells fixed with glutaraldehyde shows that the glycopeptide can bind to extracellular MHC molecules without need of internalization and processing and that the C-glycoside part does not interfere with TCR recognition. These observations constitute an important starting point for the use of this molecule as vaccine against the Tn-expressing TA3-Ha mouse mammary carcinoma.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc000143a