In the field of cancer immunotherapy, NK cells are recognized for their ability to provide a form of innate immunity against tumor cells. However, the average abundance of NK cells in the blood can be as low as 5% of the total lymphocyte population. As a result, it has been a focus to find novel therapies to expand NK cells in vitro while subsequently enhancing the cytotoxicity of these cells. Previously-defined methods include the minimal expansion of NK cells with high levels of cytokines such as IL-2 and IL-15, as well as co-culturing NK cells with feeder cell populations that are genetically modified to express NK-stimulating factors. Another method involves the use of artificially-derived plasma membrane nanoparticles (PM21) that express membrane-bound IL-21 (mb21) to successfully expand NK cells by a factor of 103 in 14 days. Exosomes, which are cell-derived vesicles naturally secreted by cancer cells, may reveal a novel way to expand NK cells and enhance their cytotoxicity by taking advantage of the exchange of genetic information within the tumor microenvironment. To test this hypothesis, NK cells have been cultured with varying concentrations of exosomes derived from modified K562-mb21-41BBl (a chronic myelogenous leukemia cell line) and shown to achieve 200-fold expansion of NK cells from other PBMCs in 14 days, a growth comparable to that of PM-21 particles. In vitro assays as well as co-culturing with various tumor cell lines will determine the cytotoxicity of these expanded cells. Potentially, exosomes may be applied as an in vivo therapy for NK cell expansion.

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