Cytochalasin B-Induced Membrane Vesicles of NK Cells for Efficient Tumor Immunotherapy

초록

Extracellular vesicles (EVs) are crucial mediators of cell-to-cell communication and contain biological components such as lipids, proteins, and nucleic acids. EVs are studied for their crucial immunomodulatory roles, particularly in natural killer (NK) cells. NK vesicles, which share surface markers and biological components with the parental NK cells, are developed as anti-cancer agents. However, their clinical application is hindered by their low productivity and an incomplete understanding of their functional mechanisms. In this study, EV-mimicking vesicles are artificially induced from NK cells by cytochalasin B treatment. These cytochalasin B-induced membrane vesicles (CIMVs) are 1.21-fold more concentrated than isolated natural EVs from NK cells (NK-EVs) and contain 1.66-fold more proteins, including those with immunological activity against tumors. The induced ARF6-positive microvesicles possess an immunological phenotype similar to that of the parental cells, while perforin, granzyme, and FasL proteins are more abundant compared to NK-EVs. Administrating NK-EVs and CIMVs to K562 and MCF-7 tumor cells induces caspase-dependent apoptosis, which leads to tumor cell cytotoxicity. These results significantly contribute to the understanding of the role of NK vesicles in cellular communication and immunity, and highlight the therapeutic potential of engineered NK-EVs via their specific action on tumor cells. Extracellular vesicles (EVs) play a pivotal role in immunomodulation, particularly in NK cells for anti-cancer therapy. Hindered by low productivity, this study introduces cytochalasin B-induced NK cell-derived vesicles (NK-CIMVs), which are 1.21-fold more concentrated and 1.66-fold richer in cytolytic proteins than NK-EVs. Mimicking parental cells, treating CIMVs induces caspase-dependent apoptosis in tumor cells, highlighting the therapeutic potential of NK-EVs for cancer therapy. image

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