Stereoselective Synthesis of Sialyl Lewis^a Antigen and the Effective Anticancer Activity of Its Bacteriophage Qβ Conjugate as an Anticancer Vaccine

Abstract

Sialyl Lewisa (sLea), also known as cancer antigen 19‐9 (CA19‐9), is a tumor associated carbohydrate antigen. The overexpression of sLea on the surface of a variety of cancer cells makes it an attractive target for anti‐cancer immunotherapy. However, sLea based anticancer vaccines have been under‐explored. To develop a new vaccine, efficient stereoselective synthesis of sLea with an amine bearing linker was achieved, which was subsequently conjugated with a powerful carrier bacteriophage Qβ. Mouse immunization with the Qβ‐sLea conjugate generated strong and long‐lasting anti‐sLea IgG antibody responses, which were superior to those induced by the corresponding conjugate of sLea with the benchmark carrier keyhole limpet hemocyanin. Antibodies elicited by Qβ‐sLea were highly selective toward sLea structure, could bind strongly with sLea expressing cancer cells and human pancreatic cancer tissues, and kill tumor cells via complement mediated cytotoxicity. Furthermore, vaccination with Qβ‐sLea significantly reduced tumor development in a metastatic cancer model in mice, demonstrating tumor protection for the first time by a sLea based vaccine highlighting the significant potential of sLea as a promising cancer antigen.