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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14 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 languageEnglish
Pages (from-to)1779-1787
Number of pages9
JournalLeukemia
Volume31
Issue number8
DOIs
Publication statusPublished - 1 Aug 2017
Externally publishedYes

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    Charmsaz, S., Al-Ejeh, F., Yeadon, T. M., Miller, K. J., Smith, F. M., Stringer, B. W., Moore, A. S., Lee, F. T., Cooper, L. T., Stylianou, C., Yarranton, G. T., Woronicz, J., Scott, A. M., Lackmann, M., & Boyd, A. W. (2017). EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia. Leukemia, 31(8), 1779-1787. https://doi.org/10.1038/leu.2016.371