Immunogenicity of benzyl alpha Thomsen-Friedenreich disaccharide using a linker on its carrier linkage

SENDRA VG, NORES GA, IRAZOQUI FJ

Pinamar, Argentina

Congreso; SAIB 41-X Congress Panamerican Association for Biochemistry and Molecular Biology (PABMB); 2005

IMMUNOGENICITY OF BENZYL ALPHA THOMSEN-FRIEDENREICH DISACCHARIDE USING A LINKER ON ITS CARRIER LINKAGE Sendra, Victor G.; Nores, Gustavo A. and Irazoqui, Fernando J. CIQUIBIC (CONICET-UNC) / Department of Biological Chemistry, Faculty of Chemical Sciences, National University of Cordoba, Argentina. E-mail: gnores@dqb.fcq.unc.edu.ar Mucin-type O-glycans are upregulated and aberrantly glycosylated in many carcinomas. O-glycan Core 1 (Galb1-3GalNAca-O-), called Thomsen-Friedenreich disaccharide (TFD), is an example of a cryptic structure that is over-expressed in cancer cells by changing its glycosyltransferase profile. This molecule is an attractive model to study carbohydrate immunogenicity and a potential candidate for active specific immunotherapy of patients with cancer. The aim of present work is study the influence of a linker in sugar conjugation of BzlaTFD to carrier protein, in the attempt to address the carbohydrate immunogenicity. As linker arm was used Lys2 and Lys5, which are covalent linkage to succinylated KLH. The synthetic glycoconjugate was used as immunogen in Balb-C mice. Antibody titers were measured by using ELISA against several antigens. They recognize BzlaTFD and related TFD structures by ELISA. Direct immunofluorescense and CellELISA evidenced that yielded IgG and IgM antibodies bind epithelial tumor cell lines (T47D, HT29 and MCF7), which are partially mediated by related TFD molecules. These antibodies have inhibitory capacity on proliferation of epithelial tumor cells. This work reveals beneficial properties on the use of Lysn as linker arm of BzlaTFD, in the attempt to direct the immune response to related TFD molecules expressed on epithelial tumor cells.