Clustering effect of Benzyl alpha Thomsen-Friedenreich disaccharide on its immunogenicity

SENDRA, VICTOR G.; NORES GUSTAVO A. AND IRAZOQUI FERNANDO J.

Puerto Iguazu. Argentina

Congreso; SAIB; 2004

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Clustering effect of Benzyl alpha Thomsen-Friedenreich disaccharide on its immunogenicity Sendra, Victor G.; Nores Gustavo A. and Irazoqui Fernando J. CIQUIBIC-CONICET / Departamento de Química Biológica, Facultad de Ciencias Químicas, U. N. C., Ciudad Universitaria, 5000 Córdoba, 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 synthetic clustered sugars with a terminal hydrophobic residue (benzyl) on the addressing of carbohydrate immunogenicity. As cluster arm was used Lys5, which is covalent linked to succinylated KLH using 1ethyl3(3dimethylaminopropyl)carbodiimide. Benzyl alpha TFD (BzlaTFD) is oxidized by using galactose oxidase and conjugated to cluster peptide (Lys5) through NaCNBH3. 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 as observed by using direct and competitive ELISA. Cell ELISA method evidenced that yielded IgG and IgM antibodies bind epithelial tumor cell lines (T47D, HT29 and TA3 Ha), which are partially mediated by related TFD molecules. The present work reveals beneficial properties on the use of Lys5 as cluster arm of BzlaTFD, with the purpose to direct the immune response to related TFD molecules expressed on epithelial tumor cells.