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The bispecific innate cell engager AFM28 eliminates CD123+ leukemic stem and progenitor cells in AML and MDS

Strategies targeting leukemic stem and progenitor cells (LSPCs) are needed for durable remissions in acute myeloid leukemia (AML) and high-risk myelodysplastic neoplasms (MDS). While CD123 constitutes a promising target on LSPCs and leukemic blasts, previous CD123-targeting approaches showed limited...

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Main Authors: Schmitt, Nanni (Author) , Siegler, Jana-Julia (Author) , Beck, Alexandra (Author) , Müller, Thomas (Author) , Kozlowska, Izabela (Author) , Sarlang, Séverine (Author) , Reusch, Uwe (Author) , Knackmuss, Stefan (Author) , Medina-Echeverz, José (Author) , Koch, Joachim (Author) , Ross, Thorsten (Author) , Darwich, Ali (Author) , Hoppe, Lea (Author) , Abba, Mohammed L. (Author) , Streuer, Alexander (Author) , Klein, Stefan (Author) , Hofmann, Wolf-Karsten (Author) , Gündner, Anna Lisa (Author) , Merz, Christian (Author) , Endell, Jan (Author) , Pahl, Jens (Author) , Nowak, Daniel (Author)
Format: Article (Journal)
Language:English
Published: 21 August 2025
In: Nature Communications
Year: 2025, Volume: 16, Pages: 1-15
ISSN:2041-1723
DOI:10.1038/s41467-025-63069-y
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-025-63069-y
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-025-63069-y
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Author Notes:Nanni Schmitt, Jana-Julia Siegler, Alexandra Beck, Thomas Müller, Izabela Kozlowska, Séverine Sarlang, Uwe Reusch, Stefan Knackmuss, José Medina-Echeverz, Joachim Koch, Thorsten Ross, Ali Darwich, Lea Hoppe, Mohammed Abba, Alexander Streuer, Stefan Klein, Wolf-Karsten Hofmann, Anna Lisa Gündner, Christian Merz, Jan Endell, Jens Pahl & Daniel Nowak
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Summary:Strategies targeting leukemic stem and progenitor cells (LSPCs) are needed for durable remissions in acute myeloid leukemia (AML) and high-risk myelodysplastic neoplasms (MDS). While CD123 constitutes a promising target on LSPCs and leukemic blasts, previous CD123-targeting approaches showed limited efficacy and challenging safety profiles. Here, we describe the preclinical efficacy and safety of the bispecific CD123/CD16A innate cell engager “AFM28”, demonstrating superior activity against AML and MDS patient-derived LSPCs and blasts in vitro compared to an Fc-enhanced CD123-targeting antibody, especially towards CD123low and/or CD64+ leukemic cells. AFM28 induces autologous anti-leukemic activity in fresh AML whole blood cultures, demonstrating its potential to enhance NK cell function from AML patients. Responsiveness can be further enhanced by allogeneic NK cell addition. Anti-leukemic activity of AFM28 is confirmed in xenograft mouse models. In addition, AFM28 is well tolerated and demonstrates pharmacodynamic activity in cynomolgus monkeys. Altogether, our results indicate that AFM28 has the potential to reduce relapse-inducing residual disease and promote long-term remissions for patients with AML and MDS with a favorable safety profile.
Item Description:Gesehen am 18.06.2026
Im Titel ist das Pluszeichen hochgestellt
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-025-63069-y

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