EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia.
S Charmsaz, F Al-Ejeh, TM Yeadon, KJ Miller, FM Smith, BW Stringer, AS Moore, F-T Lee, LT Cooper, C Stylianou, GT Yarranton, J Woronicz, AM Scott, M Lackmann, AW Boyd
Leukemia | Published : 2017
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-part..View full abstract