Chemical Synthesis of GM2 Glycans, Bioconjugation with Bacteriophage Q?, and the Induction of Anticancer Antibodies.

ABSTRACT: The development of carbohydrate-based antitumor vaccines is an attractive approach towards tumor prevention and treatment. Herein, we focused on the ganglioside GM2 tumor-associated carbohydrate antigen (TACA), which is overexpressed in a wide range of tumor cells. GM2 was synthesized chemically and conjugated with a virus-like particle derived from bacteriophage Q?. Although the copper-catalyzed azide-alkyne cycloaddition reaction efficiently introduced 237 copies of GM2 per Q?, this construct failed to induce significant amounts of anti-GM2 antibodies compared to the Q? control. In contrast, GM2 immobilized on Q? through a thiourea linker elicited high titers of IgG antibodies that recognized GM2-positive tumor cells and effectively induced cell lysis through complement-mediated cytotoxicity. Thus, bacteriophage Q? is a suitable platform to boost antibody responses towards GM2, a representative member of an important class of TACA: the ganglioside.

SUBMITTER: Yin Z 

PROVIDER: S-EPMC4726457 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature