Synthetic and immunological studies of N-acyl modified S-linked STn derivatives as anticancer vaccine candidates

It is well known that tumor cells express some aberrant glycans, termed tumor-associated carbohydrateantigens (TACAs). TACAs are good targets for the development of carbohydrate-based anticancer vaccines. However, one of the major problems is that carbohydrateantigens possess a weak immunogenicity. To tackle this problem, a number of unnatural N-modified S-linkedSTn analogues were designed and prepared. Reaction of the modified STn disaccharideswith bifunctional adipic acidp-nitrophenyl diester provided the corresponding activated esters, which was followed by the conjugation with keyhole limpet hemocyanin(KLH), affording the corresponding protein conjugates. The immunological properties of these glycoconjugateswere evaluated in a mouse model. The results showed that the modified glycoconjugatesstimulated the production of IgG antibodies that are capable of recognizing the naturally occurring STn antigen, helping the discovery of carbohydrate-based anticancer vaccine candidates.