Anti-CMV-IE EGFP0
Chapter 5- Conclusion and Outlook
Conclusion and Outlook
104
5. Conclusion and Outlook
Adaptive NK cells show a significant expansion after the resolution of CMV reactivation, when the T cell compartment retracts. In addition, in vitro expanded adaptive NK cells were able to eliminate CMV-infected target cells effectively and showed significantly increased T cell recruitment capacity under the same conditions. This suggests that adaptive NK cells and CMV-CTLs may have complementary roles: adaptive NK cells may be responsible for the initiation of CMV-CTL response and may play an important role in triggering memory CMV-CTLs thus contributing to the surveillance of CMV reactivation.
This would mean that during CMV reactivation, adaptive NK cells could be responsible for the initial control of the reactivation while (memory) CMV-CTLs are recruited and initiate their clonal expansion. Furthermore, adaptive NK cells have a unique secretory profile of cytokines, chemokines and growth factor. The profile differs significantly from non-adaptive NK cells and is also altered during stimulation of adaptive NK cells with CMV-infected target cells.
Our data suggest that adaptive NK cells could be used as protection or booster against CMV reactivation. Since NK cells are rather short lived cells they may present an adequate cell type for the currently vastly investigated transfer of chimeric antigen receptors (CAR).
Transduction of CAR directed against leukemic or cellular antigens (e.g. minor histocompatibility antigens) may provide an alternative to the current CAR-T cell production.
Allogeneic NK cells offer some advantages in comparison to CAR-T cells, such as a shorter persistency in vivo and a possible additional graft-versus-leukemia effect (GvL) in the
Conclusion and Outlook
105 haploidentical setting by choosing NK cell donors in the GvL direction [252,253]. Moreover, several recent studies showed that CAR-T cell therapy may not always be effective as downregulation of the CAR-targeted antigens occur [254]. T and NK cells secrete different arrays of cytokines, therefore, the addition of adaptive NK cells to T cell therapies could be a complementary therapeutic approach. Furthermore, CAR-engineered NK cells are able to preserve their activating and inhibitory receptors expression, which will preserve their natural cytotoxicity/anti-leukemic effect in case of target antigen downregulation [255].
Taken together, this cell type harbors an array of possibilities for exploitation.
106
Chapter 6- Appendix
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