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 var...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 var- ious 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 cyto- toxic cell-mediated immunotherapies are urgently nee- ded. 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 for- mation 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 can- cer 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-medi- ated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.展开更多
文摘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 var- ious 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 cyto- toxic cell-mediated immunotherapies are urgently nee- ded. 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 for- mation 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 can- cer 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-medi- ated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.
