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Title: | EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia. | Austin Authors: | Charmsaz, S;Al-Ejeh, F;Yeadon, T M;Miller, K J;Smith, F M;Stringer, B W;Moore, A S;Lee, Fook-Thean;Cooper, L T;Stylianou, C;Yarranton, G T;Woronicz, J;Scott, A M;Lackmann, M;Boyd, A W | Affiliation: | Leukaemia Foundation of Queensland Laboratory, QIMR-Berghofer Medical Research Institute, Brisbane, QLD, Australia Department of Medicine, University of Queensland, Brisbane, QLD, Australia Department of Surgery, Royal College of Surgeons, Dublin, Ireland, UK Personalised Medicine Team, QIMR-Berghofer Medical Research Institute, Brisbane, QLD, Australia University of Queensland Diamantina Institute and UQ Child Health Research Centre, The University of Queensland, Brisbane, Australia Oncology Service Children's Health Queensland Hospital and Health Service, Brisbane, QLD, Australia Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia KaloBios Pharmaceuticals Inc., Brisbane, CA, USA Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia |
Issue Date: | Aug-2017 | Date: | 2016-12-06 | Publication information: | Leukemia 2017; 31(8): 1779-1787 | 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 213Bismuth payload. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/17648 | DOI: | 10.1038/leu.2016.371 | Journal: | Leukemia | PubMed URL: | 27922598 | Type: | Journal Article |
Appears in Collections: | Journal articles |
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