Journal article
Synthesis and use of 6,6,6-trifluoro-L-fucose to block core-fucosylation in hybridoma cell lines
NC McKenzie, NE Scott, A John, JM White, ED Goddard-Borger
Carbohydrate Research | ELSEVIER SCI LTD | Published : 2018
Abstract
Many monoclonal antibodies (mAbs) used in cancer immunotherapy mediate tumour cell lysis by recruiting natural killer (NK) cells; a phenomenon known as antibody-dependent cellular cytotoxicity (ADCC). Eliminating core-fucose from the N-glycans of a mAb enhances its capacity to induce ADCC. As such, inhibitors of fucosylation are highly desirable for the production of mAbs for research and therapeutic use. Herein, we describe a simple synthesis of 6,6,6-trifluoro-L-fucose (F3Fuc), a metabolic inhibitor of fucosylation, and demonstrate the utility of this molecule in the production of low-fucose mAbs from murine hybridoma cell lines.
Grants
Awarded by Veski
Funding Acknowledgements
The authors thank Kaye Wycherley and Paul Masendycz for providing the hybridoma cells lines used in this research. They also acknowledge support from the Australian Cancer Research Foundation, Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. This work was facilitated by a NHMRC project grant (APP1100164) awarded to NES. NCM and AJ were supported by an Australian Postgraduate Award, NES was supported by a NHMRC CJ Martin Fellowship (1037373) and EDG-B was supported by a VESKI Innovation Fellowship.