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: Lei Qiu, Xi Gong, Qianli Wang, Jie Li, Honggang Hu, Qiuye Wu, Junping Zhang, Zhongwu Guo
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 61 Issue 11 Pg. 2045-54 (Nov 2012) ISSN: 1432-0851 [Electronic] Germany
• PMID: 22539085 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antigens, Tumor-Associated, Carbohydrate
• Antineoplastic Agents
• Cancer Vaccines
• G(M3) Ganglioside
• Hexosamines
• N-phenylacetylmannosamine
• Vaccines, Synthetic

Topics

• Animals
• Antigens, Tumor-Associated, Carbohydrate (immunology, therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Cancer Vaccines (chemical synthesis, immunology, therapeutic use)
• Cell Engineering
• Cell Line, Tumor
• Female
• G(M3) Ganglioside (analogs & derivatives, chemical synthesis, immunology)
• Hexosamines (therapeutic use)
• Immunotherapy
• Leukemia (immunology, mortality, therapy)
• Mice
• Mice, Inbred C57BL
• T-Lymphocytes (drug effects, immunology)
• Treatment Outcome
• Vaccines, Synthetic (immunology, therapeutic use)