EphA3 pay-loaded antibody therapeutics for the treatment of glioblastoma

Carolin Offenhäuser; Fares Al-Ejeh; Simon Puttick; Kathleen S. Ensbey; Zara C. Bruce; Paul R. Jamieson; Fiona M. Smith; Brett W. Stringer; Benjamin Carrington; Adrian V. Fuchs; Craig A. Bell; Rosalind Jeffree; Stephen Rose; Kristofer J. Thurecht; Andrew W. Boyd; Bryan W. Day

doi:10.3390/cancers10120519

EphA3 pay-loaded antibody therapeutics for the treatment of glioblastoma

Carolin Offenhäuser, Fares Al-Ejeh, Simon Puttick, Kathleen S. Ensbey, Zara C. Bruce, Paul R. Jamieson, Fiona M. Smith, Brett W. Stringer, Benjamin Carrington, Adrian V. Fuchs, Craig A. Bell, Rosalind Jeffree, Stephen Rose, Kristofer J. Thurecht, Andrew W. Boyd, Bryan W. Day

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Abstract

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.

Original language	English
Article number	519
Number of pages	15
Journal	Cancers
Volume	10
Issue number	12
DOIs	https://doi.org/10.3390/cancers10120519
Publication status	Published - 17 Dec 2018
Externally published	Yes

Bibliographical note

©2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open accessarticle distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Keywords

Antibody drug conjugate
EphA3
Glioblastoma
Radioimmunotherapy
Stem cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Offenhauser_EphA3_P2018Final published version, 2.7 MBLicence: CC BY

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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. (2018). EphA3 pay-loaded antibody therapeutics for the treatment of glioblastoma. Cancers, 10(12), Article 519. https://doi.org/10.3390/cancers10120519

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abstract = "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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N2 - 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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EphA3 pay-loaded antibody therapeutics for the treatment of glioblastoma

Abstract

Bibliographical note

Keywords

UN SDGs

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