Combined Role of Interleukin-15 Stimulated Natural Killer Cell-Derived Extracellular Vesicles and Carboplatin in Osimertinib-Resistant H1975 Lung Cancer Cells with EGFR Mutations

This publication evaluates extracellular vesicles (EVs) derived from IL?15 stimulated natural killer (NK) cells as therapeutic agents against osimertinib-resistant EGFR-mutant lung cancer. NK cells were expanded in a PBS Vertical-Wheel bioreactor, stimulated with IL?15, and used to generate EVs that were characterized by nanoparticle tracking analysis, atomic force microscopy, proteomics, and marker profiling. The resulting NK-EVs contained characteristic EV markers as well as NK-associated cytotoxic proteins including perforin and granzyme B. Functional studies demonstrated cytotoxic activity against resistant lung cancer cells in both 2D and 3D cultures. When combined with carboplatin, NK-EVs enhanced anti-tumor activity and reduced tumor burden in xenograft models. The study investigates mechanisms involving apoptosis, inflammatory signaling pathways, and immune checkpoint regulation while highlighting the potential of scalable NK-EV manufacturing for future immunotherapeutic applications.