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)(-)(340)OVA 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.
Peri
F
F
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, I-20126 Milano, Italy.
Cipolla
L
L
Rescigno
M
M
La Ferla
B
B
Nicotra
F
F
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000138:chemical synthesis* / Q000276:immunology / Q000494:pharmacology*; D002460:Cell Line; D003432:Cross-Linking Reagents; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D006020:Glycopeptides / Q000138:chemical synthesis / Q000276:immunology*; D006027:Glycosides / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009005:Monosaccharides / Q000737:chemistry / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D015295:Antigens, Tumor-Associated, Carbohydrate; C438934:C-glycoside; D019496:Cancer Vaccines; D003432:Cross-Linking Reagents; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006020:Glycopeptides; D006027:Glycosides; D000949:Histocompatibility Antigens Class II; D009005:Monosaccharides; C040286:Tn antigen; D010047:Ovalbumin