Journal article
Targeting of acute myeloid leukemia in vitro and in vivo with an anti-CD123 mAb engineered for optimal ADCC
SJ Busfield, M Biondo, M Wong, HS Ramshaw, EM Lee, S Ghosh, H Braley, C Panousis, AW Roberts, SZ He, D Thomas, L Fabri, G Vairo, RB Lock, AF Lopez, AD Nash
Leukemia | Published : 2014
DOI: 10.1038/leu.2014.128
Abstract
Acute myeloid leukemia (AML) is a biologically heterogeneous group of related diseases in urgent need of better therapeutic options. Despite this heterogeneity, overexpression of the interleukin (IL)-3 receptor α-chain (IL-3 Rα/CD123) on both the blast and leukemic stem cell (LSC) populations is a common occurrence, a finding that has generated wide interest in devising new therapeutic approaches that target CD123 in AML patients. We report here the development of CSL362, a monoclonal antibody to CD123 that has been humanized, affinity-matured and Fc-engineered for increased affinity for human CD16 (FcγRIIIa). In vitro studies demonstrated that CSL362 potently induces antibody-dependent cell..
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Awarded by Leukemia and Lymphoma Society
Funding Acknowledgements
We would like to the following for their contributions: Bill Panagopoulos and Melanie Pudney (IMVS), Laura McMillan, Kirstee Martin, Daria Kurtov, Matt Hardy and members of the CSL Research Department for excellent technical assistance. Naomi Sprigg for patient sample collection. Hayley Ramshaw is supported by the Peter Nelson Leukaemia Research Fund. Children's Cancer Institute Australia for Medical Research is affiliated with the University of New South Wales and the Sydney Children's Hospitals Network. Andrew Roberts is supported by funding from NHMRC (637309, 1016647) and the Leukemia and Lymphoma Society.