Stereoselective Synthesis of Sialyl Lewisa Antigen and the Effective Anticancer Activity of Its Bacteriophage Qß Conjugate as an Anticancer Vaccine

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 Qß. Mouse immunization with the Qß-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 Qß-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 Qß-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. © 2023 Wiley-VCH GmbH.

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