Exogenous Antigen Upregulation Empowers Antibody Targeted Nanochemotherapy of Leukemia
Yue Shujing1, An Jingnan2, Zhang Yifan1, Li Jiaying3, Zhao Cenzhu2, Liu Jingyi1, Liang, Lanlan, Sun Huanli1, Xu Yang2, Zhong Zhiyuan1,4
1Biomedical Polymers Laboratory College of Chemistry Chemical Engineering and Materials Science and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, P. R. China
2Jiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215123, P. R. China
3Department of Orthopaedic Surgery Orthopaedic Institute The First Affiliated Hospital, Soochow University, Suzhou 215007, P. R. China
4College of Pharmaceutical Sciences, Soochow University
Adv. Mater.2023, 2209984
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.
链接：//onlinelibrary.wiley.com/doi/10.1002/adma.202209984
