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. Author manuscript; available in PMC: 2016 Dec 1.
Published in final edited form as: Curr Opin Organ Transplant. 2015 Dec;20(6):671–680. doi: 10.1097/MOT.0000000000000243

Figure 1. Combinatorial strategies to improve NK cell adoptive immunotherapy.

Figure 1

NK cell adoptive therapy can be improved by combination approaches aimed at enhancing NK cell tumor specificity, enhancing NK cell effector capacity, and by reducing NK cell inhibition. Tumor-specificity can be increased by utilizing bispecific killer engagers (BiKE) or ADCC-optimized, tumor-specific monoclonal antibodies. NK cell effector capacity can be improved by in vitro preactivation with cytokines as well as in vivo with cytokine support, either with recombinant cytokines or with cytokine receptor super-agonists (e.g. ALT-803). Furthermore, activating receptor agonists can also be employed in vivo to improve NK cell activation and effector responses. Antibody checkpoint blockade therapy specific for inhibitory receptors expressed by NK cells will limit cell intrinsic immunosuppression. Finally, efforts to deplete regulatory T cells during NK cell adoptive therapy, e.g., using IL-2 diphtheria toxin fusion protein (IL2DT), are promising and currently under investigation.