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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

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
Journal	Cancers
Volume	10
Issue number	12
DOIs	https://doi.org/10.3390/cancers10120519
Publication status	Published - Dec 2018
Externally published	Yes

Keywords

Antibody drug conjugate
EphA3
Glioblastoma
Radioimmunotherapy
Stem cells

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10.3390/cancers10120519

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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.",

keywords = "Antibody drug conjugate, EphA3, Glioblastoma, Radioimmunotherapy, Stem cells",

author = "Carolin Offenh{\"a}user and Fares Al-Ejeh and Simon Puttick and Ensbey, {Kathleen S.} and Bruce, {Zara C.} and Jamieson, {Paul R.} and Smith, {Fiona M.} and Stringer, {Brett W.} and Benjamin Carrington and Fuchs, {Adrian V.} and Bell, {Craig A.} and Rosalind Jeffree and Stephen Rose and Thurecht, {Kristofer J.} and Boyd, {Andrew W.} and Day, {Bryan W.}",

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AU - Carrington, Benjamin

AU - Fuchs, Adrian V.

AU - Bell, Craig A.

AU - Jeffree, Rosalind

AU - Rose, Stephen

AU - Thurecht, Kristofer J.

AU - Boyd, Andrew W.

AU - Day, Bryan W.

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EphA3 pay-loaded antibody therapeutics for the treatment of glioblastoma

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Keywords

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