Institution: | 1. Department of Chemistry, Michigan State University, 48824 East Lansing, Michigan, USA
Institute for Quantitative Health Science and Engineering, Michigan State University, 48824 East Lansing, Michigan, USA
These authors contributed equally to this work.;2. Department of Chemistry, Michigan State University, 48824 East Lansing, Michigan, USA
Institute for Quantitative Health Science and Engineering, Michigan State University, 48824 East Lansing, Michigan, USA
Chemistry Department, Faculty of Science, Benha University, 13518 Benha, Qaliobiya, Egypt
These authors contributed equally to this work.;3. Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland, 21702 USA;4. Department of Chemistry, Michigan State University, 48824 East Lansing, Michigan, USA
Institute for Quantitative Health Science and Engineering, Michigan State University, 48824 East Lansing, Michigan, USA;5. Department of Surgery, Henry Ford Health System, Detroit, Michigan, 48202 USA;6. Department of Chemistry, Michigan State University, 48824 East Lansing, Michigan, USA |
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. |