AUTHOR=Glienke Wolfgang , Esser Ruth , Priesner Christoph , Suerth Julia D. , Schambach Axel , Wels Winfried S. , Grez Manuel , Kloess Stephan , Arseniev Lubomir , Koehl Ulrike TITLE=Advantages and applications of CAR-expressing natural killer cells JOURNAL=Frontiers in Pharmacology VOLUME=6 YEAR=2015 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2015.00021 DOI=10.3389/fphar.2015.00021 ISSN=1663-9812 ABSTRACT=

In contrast to donor T cells, natural killer (NK) cells are known to mediate anti-cancer effects without the risk of inducing graft-versus-host disease (GvHD). In order to improve cytotoxicity against resistant cancer cells, auspicious efforts have been made with chimeric antigen receptor (CAR) expressing T- and NK cells. These CAR-modified cells express antigen receptors against tumor-associated surface antigens, thus redirecting the effector cells and enhancing tumor-specific immunosurveillance. However, many cancer antigens are also expressed on healthy tissues, potentially leading to off tumor/on target toxicity by CAR-engineered cells. In order to control such potentially severe side effects, the insertion of suicide genes into CAR-modified effectors can provide a means for efficient depletion of these cells. While CAR-expressing T cells have entered successfully clinical trials, experience with CAR-engineered NK cells is mainly restricted to pre-clinical investigations and predominantly to NK cell lines. In this review we summarize the data on CAR expressing NK cells focusing on the possible advantage using these short-lived effector cells and discuss the necessity of suicide switches. Furthermore, we address the compliance of such modified NK cells with regulatory requirements as a new field in cellular immunotherapy.