Glycan bioengineering in immunogen design for tumor T antigen immunotargeting

SENDRA VÍCTOR G.; ZLOCOWSKI NATACHA; DITAMO YANINA; COPIOLI S.; TARP M.P.; BENNETT E.P.; CLAUSEN H.; ROTH GERMAN A.; NORES GUSTAVO A.; IRAZOQUI FERNANDO J.

Elsevier

Año: 2009 vol. 46 p. 3445 - 3445

ioengineering of GalBeta3GalNAcAlfa, known as Thomsen-Friedenreich disaccharide (TFD), is studied to promote glycan immunogenicity and immunotargeting to tumor T antigen (GalBeta3GalNAcAlfa-O-Ser/Thr). Theoretical studies on disaccharide conformations by energy minimization of structures using MM2 energy function showed that pentalysine (Lys5) linker and benzyl (Bzl) residue enhance TFD rigidity of the glycosidic bond. Antibodies raised against BzlAlfaTFD-Lys5 immunogen recognize tumor T antigen. Competitive assays confirm that TFD-related structures are the main glycan epitope. Antibodies produced by glycan bioengineering recognize HT29, T47D, MCF7, and CT26 epithelial tumor cells. Epithelial tumor cell adhesion to T antigen-binding lectins and endothelial cells was lower in the presence of antibodies raised against the engineered immunogen. The immune response directed to the bioengineered glycoconjugate inhibited CT26 tumor cell proliferation and reduced tumor growth in an in vivo