Treatment of acute myeloid leukemia models by targeting a cell surface RNA-binding protein
Menée à l'aide de modèles de xénogreffes de leucémie myéloïde aiguë, cette étude met en évidence l'activité antitumorale d'un anticorps monoclonal ciblant la nucléophosmine
Immunotherapies for acute myeloid leukemia (AML) and other cancers are limited by a lack of tumor-specific targets. Here we discover that RNA-binding proteins and glycosylated RNAs (glycoRNAs) form precisely organized nanodomains on cancer cell surfaces. We characterize nucleophosmin (NPM1) as an abundant cell surface protein (csNPM1) on a variety of tumor types. With a focus on AML, we observe csNPM1 on blasts and leukemic stem cells but not on normal hematopoietic stem cells. We develop a monoclonal antibody to target csNPM1, which exhibits robust anti-tumor activity in multiple syngeneic and xenograft models of AML, including patient-derived xenografts, without observable toxicity. We find that csNPM1 is expressed in a mutation-agnostic manner on primary AML cells and may therefore offer a general strategy for detecting and treating AML. Surface profiling and in vivo work also demonstrate csNPM1 as a target on solid tumors. Our data suggest that csNPM1 and its neighboring glycoRNA–cell surface RNA-binding protein (csRBP) clusters may serve as an alternative antigen class for therapeutic targeting or cell identification.
Nature Biotechnology , article en libre accès 2025