Molecular and structural basis for Lewis glycan recognition by a cancer-targeting antibody
Caroline Soliman, Andrew J Guy, Jia Xin Chua, Mireille Vankemmelbeke, Richard S McIntosh, Sarah Eastwood, Vi Khanh Truong, Aaron Elbourne, Ian Spendlove, Lindy G Durrant, Paul A Ramsland
BIOCHEMICAL JOURNAL | PORTLAND PRESS LTD | Published : 2020
Immunotherapy has been successful in treating many tumour types. The development of additional tumour-antigen binding monoclonal antibodies (mAbs) will help expand the range of immunotherapeutic targets. Lewis histo-blood group and related glycans are overexpressed on many carcinomas, including those of the colon, lung, breast, prostate and ovary, and can therefore be selectively targeted by mAbs. Here we examine the molecular and structural basis for recognition of extended Lea and Lex containing glycans by a chimeric mAb. Both the murine (FG88.2) IgG3 and a chimeric (ch88.2) IgG1 mAb variants showed reactivity to colorectal cancer cells leading to significantly reduced cell viability. We d..View full abstract
Awarded by LIEF Grant
This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of ANSTO, and made use of the Australian Cancer Research Foundation (ACRF) detector. This research was also undertaken using the LIEF HPC-GPGPU Facility hosted at the University of Melbourne. This Facility was established with the assistance of LIEF Grant LE170100200. This research was performed in part at the RMIT Micro Nano Research Facility (MNRF) in the Victorian Node of the Australian National Fabrication Facility (ANFF). We acknowledge the facilities, and the scientific and technical assistance of the RMIT Microscopy & Microanalysis Facility (RMMF), a linked laboratory of Microscopy Australia. CS is supported by a research training program stipend scholarship from the Australian Government, Department of Education and Training. PAR is supported by a Vice Chancellor's senior research fellowship from RMIT University.