EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia

S. Charmsaz; F. Al-Ejeh; T. M. Yeadon; K. J. Miller; F. M. Smith; B. W. Stringer; A. S. Moore; F. T. Lee; L. T. Cooper; C. Stylianou; G. T. Yarranton; J. Woronicz; A. M. Scott; M. Lackmann; A. W. Boyd

doi:10.1038/leu.2016.371

EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia

S. Charmsaz, F. Al-Ejeh, T. M. Yeadon, K. J. Miller, F. M. Smith, B. W. Stringer, A. S. Moore, F. T. Lee, L. T. Cooper, C. Stylianou, G. T. Yarranton, J. Woronicz, A. M. Scott, M. Lackmann, A. W. Boyd

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27 Citations (Scopus)

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 213 Bismuth payload.

Original language	English
Pages (from-to)	1779-1787
Number of pages	9
Journal	Leukemia
Volume	31
Issue number	8
DOIs	https://doi.org/10.1038/leu.2016.371
Publication status	Published - 1 Aug 2017
Externally published	Yes

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title = "EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia",

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 213 Bismuth payload.",

author = "S. Charmsaz and F. Al-Ejeh and Yeadon, {T. M.} and Miller, {K. J.} and Smith, {F. M.} and Stringer, {B. W.} and Moore, {A. S.} and Lee, {F. T.} and Cooper, {L. T.} and C. Stylianou and Yarranton, {G. T.} and J. Woronicz and Scott, {A. M.} and M. Lackmann and Boyd, {A. W.}",

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doi = "10.1038/leu.2016.371",

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T1 - EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia

AU - Charmsaz, S.

AU - Al-Ejeh, F.

AU - Yeadon, T. M.

AU - Miller, K. J.

AU - Smith, F. M.

AU - Stringer, B. W.

AU - Moore, A. S.

AU - Lee, F. T.

AU - Cooper, L. T.

AU - Stylianou, C.

AU - Yarranton, G. T.

AU - Woronicz, J.

AU - Scott, A. M.

AU - Lackmann, M.

AU - Boyd, A. W.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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 213 Bismuth payload.

AB - 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 213 Bismuth payload.

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SN - 0887-6924

VL - 31

SP - 1779

EP - 1787

JO - Leukemia

JF - Leukemia

IS - 8

ER -

EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia

Abstract

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