Synthetic Glycopeptides for the Construction of Anticancer Vaccines

摘要

Glycopeptides of the tandem repeat region of the tumorassociated epithelial mucin MUC1 containing tumorassociated saccharide antigens have been synthesized and conjugated to carrier proteins or T-cell epitope peptides. The T, sialyl T_N,sa2ialyl Tn, anti36gedn am-ino acid building blocks were obtained by biomimetic syntheses starting from the monosaccharide T_Nantigen conjugate. To synthesize the MUC 1 glycopeptides solid-phase methods with varied anchors were applied. Conjugation of synthetic glycopeptides to bovine serum albumin were achieved by selective reactions at squaric esters. Solid-phase fragment condensation proved successful for constructions of MUC 1 glycopeptide-T-cell epitope conjugates. Immunization of mice with a synthetic vaccine consisting of a MUC I glycopeptide and a T-cell epitope from ovalbumin induced a specific immune response. The elicited antibody only reacted with the glycopeptide. Neither its peptide nor the glycan in a different peptide were recognized. This precise differentiation by antibodies induced by chemically pure vaccines is considered promising for the development of antitumor vaccines.