Abstract
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.
Highlights
With the emergence of adoptive immune cell therapies and the generation of efficient ex vivo NK cell expansion protocols, there is a need for a translational pre-clinical model in which to test the survival, function, and safety of adoptively transferred immune cells
In this study, using CB-derived NK cells (CB-NK cells) expanded ex vivo with K562-mb-IL-21 and IL-2, we demonstrate for the first time that expanded human NK cells survive and proliferate in an autologous human immune system mouse model without the need for in vivo IL-2 administration
NK cells have proven to be a promising candidate for cancer immunotherapy, a remaining limitation of adoptive NK cell therapy is the poor in vivo survival of NK cells
Summary
Fatemeh Vahedi[1], Tina Nham[1], Sophie M. With the emergence of adoptive immune cell therapies and the generation of efficient ex vivo NK cell expansion protocols, there is a need for a translational pre-clinical model in which to test the survival, function, and safety of adoptively transferred immune cells. In this study, using CB-derived NK cells (CB-NK cells) expanded ex vivo with K562-mb-IL-21 and IL-2, we demonstrate for the first time that expanded human NK cells survive and proliferate in an autologous human immune system (humanized) mouse model without the need for in vivo IL-2 administration These results support the use of expanded NK cells as a feasible cancer therapy and provide a novel humanized model within which to test the effects of adoptively transferred cells prior to clinical application
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