EphA3 Pay-Loaded Antibody Therapeutics for the Treatment of Glioblastoma
by
Carolin Offenhäuser 1,†, Fares Al-Ejeh 1,†
, Simon Puttick 2,3, Kathleen S. Ensbey 1, Zara C. Bruce 1, Paul R. Jamieson 1, Fiona M. Smith 1, Brett W. Stringer 1, Benjamin Carrington 1, Adrian V. Fuchs 2,4, Craig A. Bell 2,4, Rosalind Jeffree 5, Stephen Rose 3, Kristofer J. Thurecht 2,4, Andrew W. Boyd 1,‡ and Bryan W. Day 1,6,*,‡
Carolin Offenhäuser 1,†, Fares Al-Ejeh 1,†, Simon Puttick 2,3, Kathleen S. Ensbey 1, Zara C. Bruce 1, Paul R. Jamieson 1, Fiona M. Smith 1, Brett W. Stringer 1, Benjamin Carrington 1, Adrian V. Fuchs 2,4, Craig A. Bell 2,4, Rosalind Jeffree 5, Stephen Rose 3, Kristofer J. Thurecht 2,4, Andrew W. Boyd 1,‡ and Bryan W. Day 1,6,*,‡
1
Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia
2
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane 4072, Australia
3
Commonwealth Scientific and Industrial Research Organisation (CSIRO), Brisbane 4006, Australia
4
Centre for Advanced Imaging, The University of Queensland, Brisbane 4072, Australia
5
Kenneth G. Jamieson Department of Neurosurgery, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
6
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane 4059, Australia
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to the manuscript.
‡
Co-Senior authors.
Cancers 2018, 10(12), 519; https://doi.org/10.3390/cancers10120519
Received: 13 November 2018 / Revised: 3 December 2018 / Accepted: 11 December 2018 / Published: 17 December 2018
(This article belongs to the Special Issue Glioblastoma: State of the Art and Future Perspectives)
The EphA3 receptor has recently emerged as a functional tumour-specific therapeutic target in glioblastoma (GBM). EphA3 is significantly elevated in recurrent disease, is most highly expressed on glioma stem cells (GSCs), and has a functional role in maintaining self-renewal and tumourigenesis. An unlabelled EphA3-targeting therapeutic antibody is currently under clinical assessment in recurrent GBM patients. In this study, we assessed the efficacy of EphA3 antibody drug conjugate (ADC) and radioimmunotherapy (RIT) approaches using orthotopic animal xenograft models. Brain uptake studies, using positron emission tomography/computed tomography (PET/CT) imaging, show EphA3 antibodies are effectively delivered across the blood-tumour barrier and accumulate at the tumour site with no observed normal brain reactivity. A robust anti-tumour response, with no toxicity, was observed using EphA3, ADC, and RIT approaches, leading to a significant increase in overall survival. Our current research provides evidence that GBM patients may benefit from pay-loaded EphA3 antibody therapies.
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Keywords:
EphA3; antibody drug conjugate; radioimmunotherapy; glioblastoma; stem cells
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MDPI and ACS Style
Offenhäuser, C.; Al-Ejeh, F.; Puttick, S.; Ensbey, K.S.; Bruce, Z.C.; Jamieson, P.R.; Smith, F.M.; Stringer, B.W.; Carrington, B.; Fuchs, A.V.; Bell, C.A.; Jeffree, R.; Rose, S.; Thurecht, K.J.; Boyd, A.W.; Day, B.W. EphA3 Pay-Loaded Antibody Therapeutics for the Treatment of Glioblastoma. Cancers 2018, 10, 519.
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