Journal article

Dianthin-30 or gelonin versus monomethyl auristatin E, each configured with an anti-calcitonin receptor antibody, are differentially potent in vitro in high-grade glioma cell lines derived from glioblastoma

R Gilabert-Oriol, SGB Furness, BW Stringer, A Weng, H Fuchs, BW Day, A Kourakis, AW Boyd, DL Hare, M Thakur, TG Johns, PJ Wookey

Cancer Immunology Immunotherapy | SPRINGER | Published : 2017

Abstract

We have reported that calcitonin receptor (CTR) is widely expressed in biopsies from the lethal brain tumour glioblastoma by malignant glioma and brain tumour-initiating cells (glioma stem cells) using anti-human CTR antibodies. A monoclonal antibody against an epitope within the extracellular domain of CTR was raised (mAb2C4) and chemically conjugated to either plant ribosome-inactivating proteins (RIPs) dianthin-30 or gelonin, or the drug monomethyl auristatin E (MMAE), and purified. In the high-grade glioma cell line (HGG, representing glioma stem cells) SB2b, in the presence of the triterpene glycoside SO1861, the EC50 for mAb2C4:dianthin was 10.0 pM and for mAb2C4:MMAE [antibody drug co..

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University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

Dr Furness was supported by the National Health and Medical Research Council of Australia (Program Grant 1055134 and Project Grant 1061044). Dr Gilabert-Oriol was supported by an Endeavour Research Fellowship (Australian Government). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors are grateful for the gift of rGelonin from Professor Rosenblum of the University of Texas MD Anderson Cancer Center, Texas, USA. Confocal microscopy was performed at the Biological Optical Microscopy Platform, The University of Melbourne (http://www.microscopy.unimelb.edu.au) and the Leibniz-Institut fur Molekulare Pharmakologie (FMP), Campus Berlin-Buch, Berlin, Germany. Thanks go to the team at the Antibody Facility (Walter and Eliza Hall Institute, Bundoora) for production of the anti-CTR antibodies.