Stereoselective Synthesis of Sialyl Lewis<sup>a</sup> Antigen and the Effective Anticancer Activity of Its Bacteriophage Qβ Conjugate as an Anticancer Vaccine
Zahra Rashidijahanabad, Sherif Ramadan, Nicholas A. O'Brien, Athar Nakisa, Shuyao Lang, Howard C. Crawford, Jeffrey C. Gildersleeve, Xuefei Huang
Abstract
Abstract 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.