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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.
AuthorsLei Qiu, Xi Gong, Qianli Wang, Jie Li, Honggang Hu, Qiuye Wu, Junping Zhang, Zhongwu Guo
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 61 Issue 11 Pg. 2045-54 (Nov 2012) ISSN: 1432-0851 [Electronic] Germany
PMID22539085 (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)

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