Dendritic cell (DC)-based vaccines for cancer are one of the most promising approaches being developed to induce protective and therapeutic anti-tumour immunity. They are unique in mobilizing multiple arms of immune responses against tumour cells (1). Migration of ex vivo generated DCs is still defective and major efforts have been done to drive DC to lymph nodes to interact with naïve T cells. However, controlling the migration destination of DCs would open new and interesting therapeutic features. Strategies to control the binding of DCs to endothelium are essential to improve their exit from bloodstream, allowing more rapid and accurate anti-tumour immune responses. Transendothelial migration is initiated by adhesive interactions, under the shear forces of blood flow, between endothelial selectins and sialofucosylated glycans, such as the sialyl Lewisx (sLex; NeuAcα2,3 Galβ1,4 [Fucα1,3] GlcNAc-R) on cell surface proteins or lipids (2). We have previously reported the expression and modulation of sLex in human DCs and found it to be modulated during the maturation of these cells. sLex augment is accompanied by increased expression of specific glycosyltransferases .
In this talk, I will show recent data from E-selectin ligands characterization and tools to improve their expression. These efforts include developing sugar analogs able be metabolized and incorporated via glycosyltransferase activity into cell surface glycans. The search for novel mimics of sLex with lower costs of synthesis and improved affinities for E-selectin is currently an important goal for cell glycoengineering. Our work bridges expertise in glycochemistry and biomedicine, to develop the first glycoengineered DC vaccine.
1. Steinman RM. 2008. Immunity 29:319-24
2. Silva Z, Konstantopoulos K, Videira PA. 2011. Annals of Biomedical Engineering
3. Silva Z, Tong Z, Guadalupe Cabral M, Martins C, Castro R, et al. 2011. 409:459-64Biochemical and biophysical research communications
