@article{acf916a08e67419bb100eaf00964a856,
title = "Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV",
abstract = "Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body{\textquoteright}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.",
keywords = "HIV, cancer, chimeric antigen receptor, immunological synapse, immunotherapy, natural killer cell",
author = "Dongfang Liu and Shuo Tian and Kai Zhang and Wei Xiong and Lubaki, {Ndongala Michel} and Zhiying Chen and Weidong Han",
note = "Funding Information: We thank Jianhua (James) Gu (director of the electron microscopy core at Houston Methodist) for the scanning electron micrograph imaging and Matthew G. Landry for the electron microscopy illustration. This work was supported in part by 1R21HL125018-01A1, 1R21AI124769-01, 1R21AI129594-01, 1R56AI130197-01, P50CA1 26752, the Houston Methodist Career Cornerstone Award, and the Baylor-UT Houston Center for AIDS Research Core Support Grant (number AI36211) from the National Institute of Allergy and Infectious Diseases. Funding Information: We thank Jianhua (James) Gu (director of the electron microscopy core at Houston Methodist) for the scanning electron micrograph imaging and Matthew G. Landry for the electron microscopy illustration. This work was supported in part by 1R21HL125018-01A1, 1R21AI124769-01, 1R21AI129594-01, 1R56AI130197-01, P50CA126752, the Houston Methodist Career Cornerstone Award, and the Baylor-UT Houston Center for AIDS Research Core Support Grant (number AI36211) from the National Institute of Allergy and Infectious Diseases. ADCC, antibody-dependent cell-mediated cytotoxicity; AML, acute myeloid leukemia; CAR, chimeric antigen receptor; CTLs, cytotoxic T lymphocytes; HLA, human leukocyte antigen; IL, interleukin; IS, immunological synapse or immune synapse; KIR, kill-cell immunoglobulin-like receptor; MHC, major histocompatibility complex; NK, natural killer; PBMCs, peripheral blood mononuclear cells; SCID, severe combined immunodeficiency; scTv, single-chain T cell receptor variable fragment; T-ALL, T cell acute lymphoblastic leukemia; TCR, T cell receptor; TIRF, total internal reflection fluorescence Dongfang Liu, Shuo Tian, Kai Zhang, Wei Xiong, Ndongala Michel Lubaki, Zhiying Chen, and Weidong Han declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by the any of the authors. An erratum to this article is available at https://doi.org/10.1007/s13238-017-0427-1. Publisher Copyright: {\textcopyright} 2017, The Author(s).",
year = "2017",
month = dec,
day = "1",
doi = "10.1007/s13238-017-0415-5",
language = "English (US)",
volume = "8",
pages = "861--877",
journal = "Protein and Cell",
issn = "1674-800X",
publisher = "Springer-Verlag GmbH and Co. KG",
number = "12",
}