Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 15, Issue 24, Pages 7561-7567Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2007.09.005
Keywords
cancer immunotherapy; cell glycoengineering; GM3; melanoma
Funding
- NCI NIH HHS [R01 CA095142-03, R01 CA95142, R01 CA095142-05, R01 CA095142-01, R01 CA095142-04, R01 CA095142-02, R01 CA095142, R01 CA095142-06] Funding Source: Medline
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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. (c) 2007 Elsevier Ltd. All rights reserved.
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