EphA3 as a Target for Antibody Immunotherapy in Acute Lymphoblastic Leukemia

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 -particle-emitting 213Bismuth payload.

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Charmsaz S, Al-Ejeh F, Yeadon TM, Miller KJ, Smith FM, Stringer BW, Moore AS, Lee FT, Cooper LT, Stylianou C, Yarranton GT, Woronicz J, Scott AM, Lackmann M, Boyd AW