Exogenous Antigen Upregulation Empowers Antibody Targeted Nanochemotherapy of Leukemia
Shujing Yue, Jingnan An, Yifan Zhang, Jiaying Li, Cenzhu Zhao, Jingyi Liu, Lanlan Liang, Huanli Sun, Yang Xu, Zhiyuan Zhong
Abstract
Acute myeloid leukemia (AML) is afflicted by a high-mortality rate and few treatment options. The lack of specific surface antigens severely hampers the development of targeted therapeutics and cell therapy. Here, it is shown that exogenous all-trans retinoic acid (ATRA) mediates selective and transient CD38 upregulation on leukemia cells by up to 20-fold, which enables high-efficiency targeted nanochemotherapy of leukemia with daratumumab antibody-directed polymersomal vincristine sulfate (DPV). Strikingly, treatment of two CD38-low expressing AML orthotopic models with ATRA and DPV portfolio strategies effectively eliminates circulating leukemia cells and leukemia invasion into bone marrow and organs, leading to exceptional survival benefits with 20-40% of mice becoming leukemia-free. The combination of exogenous CD38 upregulation and antibody-directed nanotherapeutics provides a unique and powerful targeted therapy for leukemia.