Alizadeh Zeinabad, Hojjat; Yeoh, Wen Jie; Arif, Maryam; Lomora, Mihai; Banz, Yara; Riether, Carsten; Krebs, Philippe; Szegezdi, Eva (2023). Natural killer cell-mimic nanoparticles can actively target and kill acute myeloid leukemia cells. Biomaterials, 298(122126), p. 122126. Elsevier 10.1016/j.biomaterials.2023.122126
|
Text
s41467-023-37470-4.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (6MB) | Preview |
Natural killer (NK) cells play a crucial role in recognizing and killing emerging tumor cells. However, tumor cells develop mechanisms to inactivate NK cells or hide from them. Here, we engineered a modular nanoplatform that acts as NK cells (NK cell-mimics), carrying the tumor-recognition and death ligand-mediated tumor-killing properties of an NK cell, yet without being subject to tumor-mediated inactivation. NK cell mimic nanoparticles (NK.NPs) incorporate two key features of activated NK cells: cytotoxic activity via the death ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and an adjustable tumor cell recognition feature based on functionalization with the NK cell Fc-binding receptor (CD16, FCGR3A) peptide, enabling the NK.NPs to bind antibodies targeting tumor antigens. NK.NPs showed potent in vitro cytotoxicity against a broad panel of cancer cell lines. Upon functionalizing the NK.NPs with an anti-CD38 antibody (Daratumumab), NK.NPs effectively targeted and eliminated CD38-positive patient-derived acute myeloid leukemia (AML) blasts ex vivo and were able to target and kill CD38-positive AML cells in vivo, in a disseminated AML xenograft system and reduced AML burden in the bone marrow compared to non-targeted, TRAIL-functionalized liposomes. Taken together, NK.NPs are able to mimicking key antitumorigenic functions of NK cells and warrant their development into nano-immunotherapeutic tools.
Actions (login required)
 |
Edit item |