A cancer vaccine based on N-linked sialyl-Tn antigen elicits robust and selective antitumor immunity

Cancer vaccines hold great promise for cancer prevention and treatment. Tumor-associated carbohydrate antigens (TACAs) are attractive targets for cancer vaccine development, yet suffer from their inherent weak immunogenicity. We report herein an approach based on the modification of sugar antigen structures to enhance the antitumor immunity of cancer vaccines. Novel N(OMe) -linked STn analogues have been synthesized and conjugated with carrier protein KLH to make glycoconjugates. Among them, N(OMe) -STn-KLH elicites much higher IgG antibody titers than the native STn-KLH conjugate. In a murine lung cancer metastasis model, immunization of the new vaccine results in strong protective effects against tumor including prolonged survival time and reduced tumor burden of lungs. The detailed antitumor mechanism including T cell responses, antibody responses, specific binding and antibody-mediated cytotoxicity against STn-expressing tumor cells, has been studied. Our results suggest N(OMe) -linkage may represent a new effective modification for the development of carbohydrate-based cancer vaccines and could find wide applications. New N(OMe) -linked STn analogue was synthesized and conjugated with carrier protein KLH to generate new cancer vaccine candidate. It elicited much higher IgG antibody titers than the native STn-KLH and induced much enhanced antitumor immunity in a murine lung cancer metastasis model. Robust protective effects against tumor such as prolonged survival time was observed and the antitumor mechanism was studied.