Safety and Biodistribution of NK Cell-Based Immunotherapy in Healthy and Cancer-Bearing Humanized-BLT Mice.

Natural killer (NK) cells are long known for their anti-cancer function; however, their use in clinical trials has not been well-positioned yet due to the lack of reliable methods to augment their expansion and anti-tumor potential. In our previous publications, we have demonstrated the methodology to enhance the number and function of NK cells by co-culturing peripheral blood-derived NK cells with osteoclasts (OCs) and sonicated probiotic bacteria (sAJ2). Due to significantly increased potency, these NK cells were named supercharged NK (sNK) cells. sNK cells have significantly high anti-tumor activity as well as increased cell proliferation and survival. In the current study, we present data to support the evidence that sNK cells specifically target cancer cells and not primary immune cells. We also demonstrate that sNK cells circulated to humanized-BLT (hu-BLT) mice tissues when mice were adoptively transferred, and resulted in no toxicity or visible adverse effects. However, they increased the percentages of NK cells in the peripheral blood of the mice, which may contribute to restoring the functional loss of autologous NK cells, allowing the patient's NK cells to become functional. These attributes of sNK cells make these cells not only a unique population of NK cells but also cells that can effectively be used in clinical trials of cancer patients. Overall, the data shown in this study suggest that sNK cells have potential for clinical trial applications.