Rhamnose Glycoconjugates for the Recruitment of Endogenous Anti‐Carbohydrate Antibodies to Tumor Cells

Abstract Immunotherapy is a promising strategy for targeting tumors. One emerging approach is to harness the immune effector functions of natural antibodies to destroy tumor cells. Dinitrophenyl (DNP) and the galactose‐α‐1,3‐galactose (αGal) epitope are two haptens that bind endogenous antibodies. One potential alternative is the deoxysugar L ‐rhamnose. We compared these candidates by using a biosensor assay to evaluate human sera for endogenous antibody concentration, antibody isotype distribution, and longevity of antibody–hapten interactions. Antibodies recognizing α‐rhamnose are of equal or greater abundance and affinity as those recognizing αGal. Moreover, both rhamnose and αGal epitopes are more effective than DNP at recruiting the IgG antibody subtype. Exposure of tumor cells to rhamnose‐bearing glycolipids and human serum promotes complement‐mediated cytotoxicity. These data highlight the utility of α‐rhamnose‐containing glycoconjugates to direct the immune system to target cells.