期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 -, 期 -, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202309744
关键词
Glycosylation; Sialyl Lewis(a); Stereoselective Synthesis; Tumor Protection; Vaccines
Researchers have successfully developed a sLe(a)-based anticancer vaccine, which generated strong and long-lasting antibody responses in mice, selectively killed cancer cells, and significantly reduced tumor development.
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, sLea-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, Q beta. Mouse immunization with the Q beta-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 Q beta-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 Q beta-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.
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