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Advantages and Applications of CAR-Expressing Natural Killer Cells

By Wolfgang eGlienke, Ruth eEsser, Christoph ePriesner, Julia eSuerth, Axel eSchambach, Winfried eWels, Manuel eGrez, Stephan eKloess, Lubomir eArseniev and Ulrike eKoehl

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

Topics: NK cells, T cells, GvHD, CAR, Suicide Genes, Therapeutics. Pharmacology, RM1-950
Publisher: Frontiers Media S.A.
Year: 2015
DOI identifier: 10.3389/fphar.2015.00021
OAI identifier: oai:doaj.org/article:126ae62c2bbe420ea6a6d75ab886f8db
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