Using natural killer cell‐derived exosomes as a cell‐free therapy for leukemia
Aladin Samara, Michael Anbar, Saar Shapira, Anna Zemlyansky, Alla Zozovsky, Pia Raanani, Galit Granot, Uri Rozovski
Abstract
Abstract Natural killer (NK) cells are components of the innate immune system which play a pivotal role in cancer cell surveillance. Despite promising results in clinical trials, the use of NK‐based therapies is limited due to unsatisfactory efficiencies and safety issues. In recent years, exosomes have emerged as a powerful, natural therapeutic tool. Since exosomes are known to carry cargos that reflect the cellular makeup of their cell of origin, we were prompted to test whether NK‐derived exosomes (NK exo ) maintain the anti‐leukemia capacity of NK‐cells. We found NK92MI‐cells to secrete large amounts of 100–200 nm cap‐shaped particles expressing exosomal and NK biomarkers (CD63, CD81, CD56). We demonstrated that NK exo exert a potent, selective, anti‐leukemia effect on all leukemia cell‐lines tested. Furthermore, NK exo eliminated leukemia cells isolated from patients with acute and chronic leukemia and inhibited hematopoietic colony growth. While leukemia cells were targeted and severely affected by NK exo , healthy B‐cells remained unaffected, indicating a selective effect. This selectivity was further confirmed by demonstrating that NK exo were specifically taken up by leukemic cells but not by healthy B‐cells. Our in vivo data support our in vitro and ex vivo findings and demonstrate improved human‐CD45 + leukemia blast counts and overall survival in NK exo treated humanized acute myeloid leukemia (HL‐60) xenograft mice thus supporting the assumption that NK exo possess an anti‐leukemia effect. Pending further analyses, our findings provide the pre‐clinical evidence needed to test the NKe xo approach in future pre‐clinical and clinical studies to ultimately develop an acellular “off‐the‐shelf” product to treat leukemia.