title: EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia.
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-emitting213Bismuth payload.
authors.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.
authors.forename: S
authors.initials: S
authors.lastname: Charmsaz
authors.affiliation: Personalised Medicine Team, QIMR-Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Al-Ejeh
authors.affiliation: Leukaemia Foundation of Queensland Laboratory, QIMR-Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: T M
authors.initials: TM
authors.lastname: Yeadon
authors.affiliation: Leukaemia Foundation of Queensland Laboratory, QIMR-Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: K J
authors.initials: KJ
authors.lastname: Miller
authors.affiliation: Leukaemia Foundation of Queensland Laboratory, QIMR-Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: F M
authors.initials: FM
authors.lastname: Smith
authors.affiliation: Leukaemia Foundation of Queensland Laboratory, QIMR-Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: B W
authors.initials: BW
authors.lastname: Stringer
authors.affiliation: 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.
authors.forename: A S
authors.initials: AS
authors.lastname: Moore
authors.affiliation: Olivia Newton-John Cancer Research Institute and School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia.
authors.forename: F-T
authors.initials: FT
authors.lastname: Lee
authors.affiliation: Leukaemia Foundation of Queensland Laboratory, QIMR-Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: L T
authors.initials: LT
authors.lastname: Cooper
authors.affiliation: Leukaemia Foundation of Queensland Laboratory, QIMR-Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Stylianou
authors.affiliation: KaloBios Pharmaceuticals Inc., Brisbane, CA, USA.
authors.forename: G T
authors.initials: GT
authors.lastname: Yarranton
authors.affiliation: KaloBios Pharmaceuticals Inc., Brisbane, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Woronicz
authors.affiliation: Olivia Newton-John Cancer Research Institute and School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Scott
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Lackmann
authors.affiliation: Leukaemia Foundation of Queensland Laboratory, QIMR-Berghofer Medical Research Institute, Brisbane, QLD, Australia.|Department of Medicine, University of Queensland, Brisbane, QLD, Australia.
authors.forename: A W
authors.initials: AW
authors.lastname: Boyd
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001729:Bismuth; D045744:Cell Line, Tumor; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D036121:Receptor, EphA3 / Q000276:immunology* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D036121:Receptor, EphA3; D001729:Bismuth