Exogenous Antigen Upregulation Empowers Antibody Targeted Nanochemotherapy of Leukaemia.

Acute myeloid leukaemia (AML) is afflicted by high mortality rate and few treatment options. The lack of specific surface antigens severely hampers the development of targeted therapeutics and cell therapy. Here, we show that exogenous all-trans retinoic acid (ATRA) mediates selective and transient CD38 upregulation on leukaemia cells by up to 20 folds, which enables high-efficiency targeted nanochemotherapy of leukaemia with daratumumab antibody-directed polymersomal vincristine sulfate (DPV). Strikingly, treatment of two CD38-low expressing AML orthotopic models with ATRA and DPV portfolio strategy effectively eliminates circulating leukaemia cells and leukaemia invasion into bone marrow and organs, leading to exceptional survival benefits with 20-40% mice becoming leukaemia-free. The combination of exogenous CD38 upregulation and antibody-directed nanotherapeutics provides a unique and powerful targeted therapy for leukaemia. This article is protected by copyright. All rights reserved.