Enhanced immune recognition of cryptic glycan markers in human tumors

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Item Type:	Article
Title:	Enhanced immune recognition of cryptic glycan markers in human tumors
Creators Name:	Newsom-Davis, T.E., Wang, D., Steinman, L., Chen, P.F.T., Wang, L.X., Simon, A.K. and Screaton, G.R.
Abstract:	Abnormal glycosylation is one of the hallmarks of the cancer cell and is associated with tumor invasion and metastasis. The development of tumor-associated carbohydrate antigen (TACA) vaccines has been problematic due to poor immunogenicity. However, when appropriate targets can be identified, passive immunization with monoclonal antibodies (mAbs) directed against TACAs has been shown to have antitumor activity. Fas ligand (FasL) is a transmembrane protein that induces apoptosis in cells expressing its receptor, Fas. When grafted into mice, FasL-expressing tumor cells break immunologic tolerance to self-antigens and induce antibody-mediated tumor immunity. Here, five IgM mAbs were produced from mice vaccinated with FasL-expressing B16F10 mouse melanoma cells. They recognize various syngeneic and allogeneic murine tumor cell lines. One mAb, TM10, recognizes a range of human tumor cell lines, including melanoma, prostate, and ovarian cancer. It does not bind to untransformed cells. The epitopes recognized by all the mAbs were carbohydrates expressed on proteins. Using carbohydrate microarrays, the antigenic targets of TM10 were found to be high-mannose core structures of N-linked glycans. In normal cells, high-mannose clusters are hidden by extensive saccharide branching but they become exposed in cancer cells as a result of abnormal glycosylation pathways. Vaccination with FasL-expressing tumors therefore enables the immune system to break tolerance to self-antigens, allowing identification of novel TACAs that can form the basis of future humoral anticancer therapy.
Keywords:	Monoclonal Antibodies, Antibody-Dependent Cell Cytotoxicity, Carbohydrate Tumor-Associated Antigens, Tumor Cell Line, Epitopes, Fas Ligand Protein, Glycosylation, Mannose, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Mice, Inbred DBA Mice, Neoplasms, Polysaccharides, Vaccination, Animals, Mice
Source:	Cancer Research
ISSN:	0008-5472
Publisher:	American Association for Cancer Research
Volume:	69
Number:	5
Page Range:	2018-25
Date:	1 March 2009
Official Publication:	https://doi.org/10.1158/0008-5472.CAN-08-3589
PubMed:	View item in PubMed

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