Natural killer cell-mimic nanoparticles can actively target and kill acute myeloid leukemia cells

Hojjat Alizadeh Zeinabad; Wen Jie Yeoh; Maryam Arif; Mihai Lomora; Yara Banz; Carsten Riether; Philippe Krebs; Eva Szegezdi

doi:10.1016/j.biomaterials.2023.122126

Natural killer cell-mimic nanoparticles can actively target and kill acute myeloid leukemia cells

Biomaterials. 2023 Jul:298:122126. doi: 10.1016/j.biomaterials.2023.122126. Epub 2023 Apr 15.

Authors

Hojjat Alizadeh Zeinabad¹, Wen Jie Yeoh², Maryam Arif³, Mihai Lomora⁴, Yara Banz⁵, Carsten Riether⁶, Philippe Krebs⁵, Eva Szegezdi⁷

Affiliations

¹ Apoptosis Research Centre, School of Biological and Chemical Sciences, University of Galway, Galway, Ireland; Cell Stress Discoveries, University of Galway Business Innovation Centre, Galway, Ireland.
² Institute of Pathology, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland.
³ Apoptosis Research Centre, School of Biological and Chemical Sciences, University of Galway, Galway, Ireland.
⁴ School of Biological and Chemical Sciences, University of Galway, Galway, Ireland; CÚRAM, Science Foundation Ireland Research Centre for Medical Devices, University of Galway, Galway, Ireland.
⁵ Institute of Pathology, University of Bern, Bern, Switzerland.
⁶ Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷ Apoptosis Research Centre, School of Biological and Chemical Sciences, University of Galway, Galway, Ireland; CÚRAM, Science Foundation Ireland Research Centre for Medical Devices, University of Galway, Galway, Ireland. Electronic address: eva.szegezdi@universityofgalway.ie.

PMID: 37094524
DOI: 10.1016/j.biomaterials.2023.122126

Abstract

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.

Keywords: AML; Fc-binding receptor (CD16); Liposome nanoparticle; Natural killer (NK) cell; Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL); Tumor targeting.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Cytotoxicity, Immunologic
Humans
Killer Cells, Natural
Leukemia, Myeloid, Acute* / drug therapy
Ligands
Nanoparticles*
Tumor Necrosis Factor-alpha

Substances

Ligands
Tumor Necrosis Factor-alpha