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

• Published in: Angewandte Chemie 2023-11, Vol.135 (47)
• Main Authors: Rashidijahanabad, Zahra, Ramadan, Sherif, O'Brien, Nicholas A., Nakisa, Athar, Lang, Shuyao, Crawford, Howard, Gildersleeve, Jeffrey C., Huang, Xuefei
• Format: Article
• Language: English
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202309744

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