1. EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia
- Author
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Charmsaz, S, Al-Ejeh, F, Yeadon, TM, Miller, KJ, Smith, FM, Stringer, BW, Moore, AS, Lee, Fook-Thean, Cooper, LT, Stylianou, C, Yarranton, GT, Woronicz, J, Scott, Andrew, Lackmann, M, and Boyd, AW
- Subjects
Uncategorized - 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.
- Published
- 2023
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