A new strategy based on a macrophage-inducible
C-type lectin (Mincle) agonist was established to construct synthetic
cancer vaccines. Using sialyl-Tn (STn) as a model
antigen, four conjugates with the Mincle agonist as a built-in adjuvant were designed and synthesized through a facile and efficient method. All conjugates could induce BMDMs to produce inflammatory
cytokines in a Mincle-dependent manner and were found to elicit robust humoral and T cell-dependent immune responses alone in mice. The corresponding
antibodies could recognize, bind and exhibit
complement-dependent cytotoxicity to STn-positive
cancer cells, leading to
tumor cell lysis. Moreover, all conjugates could effectively inhibit
tumor growth and prolong the mice survival time in vivo, with
therapeutic effects better than STn-
CRM197/Al. Notably, compared to conventional
glycoprotein conjugate vaccines, these fully synthetic
conjugate vaccines do not cause "
epitope suppression." Mincle
ligands thus hold great potential as a platform for the development of new
vaccine carriers with self-adjuvanting properties for
cancer treatment. Preliminary structure-activity relationship analysis shows that a
vaccine containing one STn
antigen carried by
vizantin exhibits the best efficacy, providing support for further optimization and additional investigation into Mincle agonists as the carrier of self-adjuvanting
cancer vaccines.