Lindy Durrant

By Jia Xin Chua and Lindy Durrant

Glycomic profiling of tumour tissues consistently shows alterations in N- and O-glycosylation profiles of glycoproteins and glycolipids compared to healthy tissues, with important functional implications for cancer cell biology. The overexpression of tumour-associated carbohydrate antigens (TACAs), as a result of aberrant glycosylation in tumours, is usually correlated with poor prognosis and survival of cancer patients. In tumours, TACAs are associated with worse tumour progression than the deletion and inactivation of tumour suppressor genes. The findings of TACAs acting are not merely tumour markers but also constitute part of the machinery in inducing cancer metastasis and invasiveness further strengthen the scientific rationales for immunotherapy targeting TACAs. Despite the attractiveness of the TACAs, there are very few anti-glycan monoclonal antibodies (mAbs), as glycans usually induce low-affinity IgM responses. This chapter provides an overview of TACAs, direct killing anti-glycan mAbs, and introduces two murine mAbs (FG88 mAbs) that recognise Lewis carbohydrate antigens overexpressed on tumour glycoconjugates with high functional affinity. Although the production of anti-glycan mAbs against cancers is not new, the production of high-affinity IgG anti-glycan mAbs is novel. FG88 mAbs definitely have great potential in cancer therapy and serve as valuable tools in glycobiology research.

Part of the book: Carbohydrate