Recently, the team of Prof. Yueqing Gu and Prof. Siwen Li from School of Engineering, TUAT published their latest research result “A bispecific nanosystem activates endogenous natural A bispecific nanosystem activates endogenous natural killer cells in the bone marrow for haematologic malignancies therapy”. Yanqin Zhang, a postdoctoral fellow, Yanfang Deng, a master's student, and Yuewen Zhai, a doctoral student, are the co-first authors of the paper, while Prof. Yueqing Gu and Prof. Siwen Li are the co-corresponding authors. China Pharmaceutical University is the sole correspondent of this paper.
Most malignant hematological tumors are caused by uncontrolled clonal proliferation of tumor cells in the bone marrow and have high mortality and recurrence rates. Existing treatments such as chemotherapy, immunotherapy, and cellular therapy, while showing some promise in prolonging patient survival, still face challenges in specifically eliminating tumor cells from the bone marrow, mitigating toxic side effects, and preventing disease recurrence due to the lack of effective bone marrow targeting and the difficulty in reversing the bone marrow microenvironment.
In this study, the researchers reported a bispecific nanovesicle drug delivery system, using hematopoietic stem cell vesicles as bone marrow targeting carriers, which achieved bispecific capture of NK cells and tumor cells in the bone marrow by modifying them with dual ligands (aPD-L1 and aNKG2D) and encapsulating them with colony-stimulating factors (CSFs), which activated the NK cells and at the same time blocked the inhibitory effect of tumor cells on NK cells, thus contributing to the NK cell and tumor cell inhibition. NK cells and tumor cells in the bone marrow, blocking the inhibitory effect of tumor cells on NK cells while activating NK cells, thus prompting NK cells to rapidly exert tumor cell killing effects. This bispecific nanocapsule drug delivery system can not only adequately treat acute myeloid leukemia (AML) and multiple myeloma (MM), but also effectively inhibit tumor recurrence, with both therapeutic and preventive roles, which is promising for clinical application in the prevention and treatment of hematological malignancies.
This study was supported by the Outstanding Youth Fund Program of the National Natural Science Foundation of China (NSFC), and the Top-level Program of the National Natural Science Foundation of China (NSFC).
Article link: https://www.nature.com/articles/s41565-024-01736-9
