Advantages and applications of CAR-expressing natural killer cells.
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.
Institute of Cellular Therapeutics Integrated Research and Treatment Center Transplantation, Hannover Medical School Hannover, Germany.
Wolfgang
W
Glienke
Institute of Cellular Therapeutics Integrated Research and Treatment Center Transplantation, Hannover Medical School Hannover, Germany.
Ruth
R
Esser
Institute of Cellular Therapeutics Integrated Research and Treatment Center Transplantation, Hannover Medical School Hannover, Germany.
Christoph
C
Priesner
Institute of Experimental Hematology, Hannover Medical School Hannover, Germany.
Julia D
JD
Suerth
Institute of Experimental Hematology, Hannover Medical School Hannover, Germany.
Axel
A
Schambach
Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy Frankfurt am Main, Germany.
Winfried S
WS
Wels
Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy Frankfurt am Main, Germany.
Manuel
M
Grez
Institute of Cellular Therapeutics Integrated Research and Treatment Center Transplantation, Hannover Medical School Hannover, Germany.
Stephan
S
Kloess
Institute of Cellular Therapeutics Integrated Research and Treatment Center Transplantation, Hannover Medical School Hannover, Germany.
Lubomir
L
Arseniev
Institute of Cellular Therapeutics Integrated Research and Treatment Center Transplantation, Hannover Medical School Hannover, Germany.
Ulrike
U
Koehl
CAR; NK cells; T cells; suicide genes