Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents.

Carsten Riether, Thomas Pabst, Sabine Höpner, Ulrike Bacher, Magdalena Hinterbrandner, Yara Banz, Rouven Müller, Markus G. Manz, Walid H. Gharib, David Francisco, Remy Bruggmann, Luc Van Rompaey, Mahan Moshir, Tim Delahaye, Domenica Gandini, Ellen Erzeel, Anna Hultberg, Samson Fung, Hans De Haard, Nicolas Leupin & Adrian F. Ochsenbein
Acute myeloid leukemia (AML) is driven by leukemia stem cells (LSCs) that resist conventional chemotherapy and are the major cause of relapse1,2. Hypomethylating agents (HMAs) are the standard of care in the treatment of older or unfit patients with AML, but responses are modest and not durable3-5. Here we demonstrate that LSCs upregulate the tumor necrosis factor family ligand CD70 in response to HMA treatment resulting in increased CD70/CD27 signaling. Blocking CD70/CD27 signaling and targeting...
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