Efficient glycoengineering of GM3 on melanoma cell and monoclonal antibody-mediated selective killing of the glycoengineered cancer cell.

To verify the principal of a new immunotherapeutic strategy for cancer, a monoclonal antibody 2H3 against N-phenylacetyl GM3, an unnatural form of the tumor-associated antigen GM3, was prepared and employed to demonstrate that murine melanoma cell B16F0 could be effectively glycoengineered by N-phenylacetyl-d-mannosamine to express N-phenylacetyl GM3 and that 2H3 was highly cytotoxic to the glycoengineered B16F0 cell in the presence of complements. It was further demonstrated that B16F0 cell could be glycoengineered 4-5 times more effectively than 3T3 A31 cell, a normal murine embryo fibroblast cell, and that the antibody and complement mediated cytotoxicity was at least 200 times more potent to the glycoengineered B16F0 cell than to the N-phenylacetyl-d-mannosamine-treated 3T3 A31 cell. These results show the promise for developing useful melanoma immunotherapies based on vaccination against N-phenylacetyl GM3 followed by treatment with N-phenylacetyl-d-mannosamine.
AuthorsQianli Wang, Junping Zhang, Zhongwu Guo
JournalBioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 15 Issue 24 Pg. 7561-7 (Dec 15 2007) ISSN: 1464-3391 [Electronic] England
PMID17892942 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antibodies, Monoclonal
  • Antigens, Tumor-Associated, Carbohydrate
  • Antineoplastic Agents
  • G(M3) Ganglioside
  • Animals
  • Antibodies, Monoclonal (pharmacology)
  • Antigens, Tumor-Associated, Carbohydrate (chemistry, immunology, metabolism)
  • Antineoplastic Agents (chemistry, metabolism)
  • Carbohydrate Sequence
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Female
  • G(M3) Ganglioside (chemistry, immunology, metabolism)
  • Immunotherapy (methods)
  • Melanoma, Experimental (immunology, therapy)
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Molecular Sequence Data
  • Tumor Cells, Cultured

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