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Mongis A., Piller F. and Piller V.

Coupling of Immunostimulants to Live Cells through Metabolic Glycoengineering and Bioorthogonal Click Chemistry.

Bioconjugate Chemistry (2017) 28 (4) 1151-1165.

par Frapart - publié le , mis à jour le

Abstract :

The present study investigated the potential of metabolic glycoengineering followed by bioorthogonal click chemistry for introducing into cell-surface glycans different immunomodulating molecules. Mouse tumor models EG7 and MC38-OVA were treated with Ac4Ga1NAz and Ac4ManNAz followed by ligation of immunostimulants to modified cell surface glycans of the living cells through bioorthogonal click chemistry. The presence of covalently bound oligosaccharide and oligonucleotide immunostimulants could be clearly established. The activation of a reporter macrophage cell line was determined. Depending on the tumor cell line, covalently and noncovalently bound CpG activated the macrophages by between 67 and 100% over controls. EG7 cells with covalently attached immunostimulants and control injected subcutaneously into C57BL/6 mice. All tumor cells subjected to the complete treatment with control molecules formed tumors like nontreated cells confirming cell viability. However, when CpG oligonucleotide was linked to cell-surface glycans, tumor growth was slowed significantly (60% reduction, n = 10, by covalently bound CpG compared to noncovalently bound CpG, n = 10). When mice that had not developed large tumors were challenged with unmodified EG7 cells, no new tumors developed, suggesting protection through the immune system.