title: A novel cancer immunotherapy based on the combination of a synthetic carbohydrate-pulsed dendritic cell vaccine and glycoengineered cancer cells.
abstract: Immune tolerance to tumor-associated carbohydrate antigens (TACAs) has severely restricted the usefulness of most TACAs. To overcome this problem, we selected a sialylated trisaccharide TACA, GM3, as a target antigen, and tested a new immunotherapeutic strategy by combining metabolic bioengineering with dendritic cell (DC) vaccination. We engineered cancer cells to express an artificial structure, N-phenylacetyl-D-neuraminic acid, in place of the natural N-acetyl-D-neuraminic acid of GM3 by using N-phenylacetyl-D-mannosamine (ManNPhAc) as a biosynthetic precursor. Next, we selectively targeted the bioengineered cancer cells by vaccination with DCs pulsed with the GM3 N-phenylacetyl derivative. Vaccination with GM3NPhAc-KLH-loaded DCs elicited robust GM3NPhAc-specific T cell-dependent immunity. The results showed that this strategy could significantly inhibit FBL3 tumor growth and prolong the survival of tumor-bearing mice; B16F10 lung metastases could also be reduced. These findings lay out a new strategy for overcoming immune tolerance to TACAs, such as GM3, for the development of effective tumor immunotherapies.
authors.affiliation: College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qiu
authors.affiliation: College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Shichong
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States.
authors.forename: Qianli
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Qiuye
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Guo
authors.affiliation: College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D060846:Cell Engineering; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006595:Hexosamines / Q000276:immunology*; D007167:Immunotherapy; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006595:Hexosamines; C510175:N-phenylacetylmannosamine
keywords: GM3 antigen; cancer immunotherapy; cell metabolic glycoengineering; tumor-associated carbohydrate antigen