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Adoptive immune cell therapy is emerging as a promising immunotherapy for cancer. Particularly, the adoptive transfer of NK cells has garnered attention due to their natural cytotoxicity against tumor cells and safety upon adoptive transfer to patients. Although strategies exist to efficiently generate large quantities of expanded NK cells  ex vivo , it remains unknown whether these expanded NK cells can persist and/or proliferate  in vivo  in the absence of exogenous human cytokines. Here, we have examined the adoptive transfer of  ex vivo  expanded human cord blood-derived NK cells into humanized mice reconstituted with autologous human cord blood immune cells. We report that  ex vivo  expanded NK cells are able to survive and possibly proliferate  in vivo  in humanized mice without exogenous cytokine administration, but not in control mice that lack human immune cells. These findings demonstrate that the presence of autologous human immune cells supports the  in vivo  survival of  ex vivo  expanded human NK cells. These results support the application of  ex vivo  expanded NK cells in cancer immunotherapy and provide a translational humanized mouse model to test the lifespan, safety, and functionality of adoptively transferred cells in the presence of autologous human immune cells prior to clinical use.

Ex Vivo Expanded Human NK Cells Survive and Proliferate in Humanized Mice with Autologous Human Immune Cells