Work

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

Year: 2023

Type: article

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 anticancer 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 the sLea structure, could bind strongly with sLea‐expressing cancer cells and human pancreatic cancer tissues, and kill tumor cells through 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, thus highlighting the significant potential of sLea as a promising cancer antigen.

Source: Angewandte Chemie

DOI: 10.1002/ange.202309744