title: Combining synthetic carbohydrate vaccines with cancer cell glycoengineering for effective cancer immunotherapy.
abstract: Tumor-associated carbohydrate antigens (TACAs) are useful targets for the development of cancer vaccines or immunotherapies. However, a major obstacle in this application of TACAs is their poor immunogenicity. To overcome the problem, a new immunotherapeutic strategy combining synthetic vaccines made of artificial TACA derivatives and metabolic glycoengineering of cancer cells to express the artificial TACA derivatives was explored. Using a murine leukemia model FBL3 with GM3 antigen as the target, it was shown that artificial GM3 N-phenylacetyl derivative (GM3NPhAc) elicited robust antigen-specific T cell-dependent immunity and that N-phenylacetyl-D-mannosamine (ManNPhAc) as the biosynthetic precursor of GM3NPhAc selectively glycoengineered cancer cells to express GM3NPhAc both in vitro and in vivo. It was also demonstrated that GM3NPhAc-specific antisera and antibodies mediated strong cytotoxicity to ManNPhAc-treated FBL3 cell. Furthermore, vaccination with a conjugate vaccine made of GM3NPhAc followed by ManNPhAc treatment could significantly suppress tumor growth and prolong the survival of tumor-bearing mouse. These results have proved the feasibility of the new cancer immunotherapeutic strategy, as well as its efficacy to cure cancer, which is of general significance.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qiu
authors.forename: Xi
authors.initials: X
authors.lastname: Gong
authors.forename: Qianli
authors.initials: Q
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Honggang
authors.initials: H
authors.lastname: Hu
authors.forename: Qiuye
authors.initials: Q
authors.lastname: Wu
authors.forename: Junping
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use*; D060846:Cell Engineering; D045744:Cell Line, Tumor; D005260:Female; D005679:G(M3) Ganglioside / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000276:immunology; D006595:Hexosamines / Q000627:therapeutic use; D007167:Immunotherapy; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D005679:G(M3) Ganglioside; D006595:Hexosamines; C510175:N-phenylacetylmannosamine; D014614:Vaccines, Synthetic