Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV.
10.1007/s13238-017-0415-5
- Author:
Dongfang LIU
1
;
Shuo TIAN
2
;
Kai ZHANG
2
;
Wei XIONG
2
;
Ndongala Michel LUBAKI
2
;
Zhiying CHEN
2
;
Weidong HAN
3
Author Information
1. Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX, 77030, USA. dliu2@houstonmethodist.org.
2. Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX, 77030, USA.
3. Institute of Basic Medicine, College of Life Sciences, Chinese PLA General Hospital, Beijing, 100853, China. hanwdrsw69@yahoo.com.
- Publication Type:Journal Article
- Keywords:
HIV;
cancer;
chimeric antigen receptor;
immunological synapse;
immunotherapy;
natural killer cell
- MeSH:
Animals;
HIV Infections;
immunology;
therapy;
HIV-1;
immunology;
Humans;
Immunity, Cellular;
Immunological Synapses;
Immunotherapy;
Killer Cells, Natural;
transplantation;
Neoplasms;
immunology;
therapy;
Receptors, Antigen, T-Cell;
genetics;
immunology;
Recombinant Fusion Proteins;
genetics;
immunology;
T-Lymphocytes;
immunology;
transplantation
- From:
Protein & Cell
2017;8(12):861-877
- CountryChina
- Language:English
-
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 CAR-modified 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 CAR-modified 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.
