REVIEW

Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV

  • Dongfang Liu , 1,2 ,
  • Shuo Tian 1 ,
  • Kai Zhang 1 ,
  • Wei Xiong 1 ,
  • Ndongala Michel Lubaki 1 ,
  • Zhiying Chen 1 ,
  • Weidong Han , 3
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  • 1. Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA
  • 2. Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA
  • 3. Institute of Basic Medicine, College of Life Sciences, Chinese PLA General Hospital, Beijing 100853, China

Received date: 01 Mar 2017

Accepted date: 22 Apr 2017

Published date: 27 Dec 2017

Copyright

2017 The Author(s) 2017. This article is an open access publication

Abstract

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body’s immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CARmodified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use. To alleviate these disadvantages of CAR-modified T cell immunotherapy, additional cytotoxic cell-mediated immunotherapies are urgently needed. The unique biology of NK cells allows them to serve as a safe, effective, alternative immunotherapeutic strategy to CAR-modified T cells in the clinic. While the fundamental mechanisms underlying the cytotoxicity and side effects of CAR-modified T and NK cell immunotherapies remain poorly understood, the formation of the immunological synapse (IS) between CARmodified T or NK cells and their susceptible target cells is known to be essential. The role of the IS in CAR T and NK cell immunotherapies will allow scientists to harness the power of CAR-modified T and NK cells to treat cancer and infectious diseases. In this review, we highlight the potential applications of CAR-modified NK cells to treat cancer and human immunodeficiency virus (HIV), and discuss the challenges and possible future directions of CAR-modified NK cell immunotherapy, as well as the importance of understanding the molecular mechanisms of CAR-modified T cell- or NK cell-mediated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.

Cite this article

Dongfang Liu , Shuo Tian , Kai Zhang , Wei Xiong , Ndongala Michel Lubaki , Zhiying Chen , Weidong Han . Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV[J]. Protein & Cell, 2017 , 8(12) : 861 -877 . DOI: 10.1007/s13238-017-0415-5

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