EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia
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Al-Ejeh, F
Yeadon, TM
Miller, KJ
Smith, FM
Stringer, BW
Moore, AS
Lee, F-T
Cooper, LT
Stylianou, C
Yarranton, GT
Woronicz, J
Scott, AM
Lackmann, M
Boyd, AW
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Abstract
The human EphA3 gene was discovered in a pre-B acute lymphoblastic leukemia (pre-B-ALL) using the EphA3-specific monoclonal antibody (mAb), IIIA4, which binds and activates both human and mouse EphA3. We use two models of human pre-B-ALL to examine EphA3 function, demonstrating effects on pre-B-cell receptor signaling. In therapeutic targeting studies, we demonstrated antitumor effects of the IIIA4 mAb in EphA3-expressing leukemic xenografts and no antitumor effect in the xenografts with no EphA3 expression providing evidence that EphA3 is a functional therapeutic target in pre-B-ALL. Here we show that the therapeutic effect of the anti-EphA3 antibody was greatly enhanced by adding an α-particle-emitting 213Bismuth payload.
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Leukemia
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31
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8
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© The Author(s) 2017. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
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Cardiovascular medicine and haematology
Clinical sciences
Oncology and carcinogenesis
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Life Sciences & Biomedicine
Oncology
Hematology
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Charmsaz, S; Al-Ejeh, F; Yeadon, TM; Miller, KJ; Smith, FM; Stringer, BW; Moore, AS; Lee, F-T; Cooper, LT; Stylianou, C; Yarranton, GT; Woronicz, J; Scott, AM; Lackmann, M; Boyd, AW, EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia, Leukemia, 2017, 31 (8), pp. 1779-1787