Abstract
Immunotherapies based on natural killer (NK) cells are among the most promising therapies under development for the treatment of so far incurable forms of leukemia and other types of cancer. The importance of NK cells for the control of viral infections and cancer is supported among others by the findings that viruses and tumors use a multitude of mechanisms to subvert and evade the NK cell system. Infections and malignant diseases can further lead to the shaping of NK cell populations with altered reactivity. Counter measures of potential therapeutic impact include the blocking of inhibitory interactions between NK cell receptors and their cellular ligands, the enhancement of activating receptor signals, and the infusion of large numbers of ex vivo generated and selected NK cells. Moreover, the specific cross-linking of NK cells to their target cells using chimeric antigen receptors or therapeutic bi-/trispecific antibody reagents is a promising approach. In this context, NK cells stand out by their positive effects and safety demonstrated in most clinical trials so far. Based in part on results of the recent EC-sponsored project “NATURIMMUN” and considering additional published work in the field, we discuss below new developments and future directions that have the potential to further advance and establish NK cell-based therapies at the clinics on a broader scale.
Highlights
Natural killer (NK) cells have been classically defined as part of the innate immune system providing immediate reactivity against their main targets, virally infected and tumor cells [1]
Taken together with clinical NK infusion trials in leukemia patients, which have shown exciting antitumor activities and generally safety of the procedure [11,12,13], it appears that NK cells could be the cells of choice in cellular therapies of leukemia not displaying the critical graft versus host activities of T lymphocytes
In regard of acute myeloid leukemia (AML), we investigated within the NATURIMMUN project NK cells in patients receiving a novel maintenance therapy with histamine plus IL-2
Summary
Natural killer (NK) cells have been classically defined as part of the innate immune system providing immediate reactivity against their main targets, virally infected and tumor cells [1]. A new model was developed in the NATURIMMUN project using mice that lack the Flt receptor [55] and display reduced murine myeloid differentiation In these mice, human dendritic cells and human NK cells could be successfully boosted by human Flt ligand providing a novel mouse model with increased NK cell numbers [(56), this research topic]. Significant inhibition of tumor growth and improvement of survival rates were observed These results provide a rationale for NK infusion therapies for leukemia and for solid cancer treatment [(44), this research topic]. Clinical trials of NK infusion therapies, performed mostly in different forms of leukemia, have uniformly shown safety of infused NK cells and in certain cases exciting effects on disease-free survival [11] This together underlines the feasibility and potential efficacy of NK cell-based immunotherapies. In light of the high need of new therapies for solid cancers these should be pursued
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
