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.