Review article

Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy

Authors: Yuan HU1, Zhi-gang TIAN2, Cai ZHANG1
1 Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Ji-nan 250012, China
2 Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei 230026, China
Corresponding to: Zhi-gang TIAN: tzg@ustc.edu.cn, Cai ZHANG: caizhangsd@sdu.edu.cn,
DOI: 10.1038/aps.2017.125
Received: 17 April 2017
Accepted: 6 June 2017
Advance online: 7 September 2017

Abstract

Abstract
Natural killer (NK) cells are potential effector cells in cell-based cancer immunotherapy, particularly in the control of hematological malignancies. The chimeric antigen receptor (CAR) is an artificially modified fusion protein that consists of an extracellular antigen recognition domain fused to an intracellular signaling domain. T cells genetically modified with a CAR have demonstrated remarkable success in the treatment of hematological cancers. Compared to T cells, CAR-transduced NK cells (CAR-NK) exhibit several advantages, such as safety in clinical use, the mechanisms by which they recognize cancer cells, and their abundance in clinical samples. Human primary NK cells and the NK-92 cell line have been successfully transduced to express CARs against both hematological cancers and solid tumors in pre-clinical and clinical trials. However, many challenges and obstacles remain, such as the ex vivo expansion of CARmodified primary NK cells and the low transduction efficiency of NK cells. Many strategies and technologies have been developed to improve the safety and therapeutic efficacy in CAR-based immunotherapy. Moreover, NK cells express a variety of activating receptors (NKRs), such as CD16, NKG2D, CD226 and NKp30, which might specifically recognize the ligands expressed on tumor cells. Based on the principle of NKR recognition, a strategy that targets NKRs is rapidly emerging. Given the promising clinical progress described in this review, CAR- and NKR-NK cell-based immunotherapy are likely promising new strategies for cancer therapy.
Keywords: chimeric antigen receptor; natural killer cells; cancer immunotherapy