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Genetic reprogramming for NK cell cancer immunotherapy with CRISPR/Cas9
Author(s) -
Afolabi Lukman O.,
Adeshakin Adeleye O.,
Sani Musbahu M.,
Bi Jiacheng,
Wan Xiaochun
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13094
Subject(s) - crispr , genome editing , reprogramming , biology , chimeric antigen receptor , immunotherapy , cancer immunotherapy , cas9 , cytotoxic t cell , acquired immune system , cancer research , computational biology , cell , immunology , antigen , immune system , gene , genetics , in vitro
Summary Natural killer cells are potent cytotoxic lymphocytes specialized in recognizing and eliminating transformed cells, and in orchestrating adaptive anti‐tumour immunity. However, NK cells are usually functionally exhausted in the tumour microenvironment. Strategies such as checkpoint blockades are under investigation to overcome NK cell exhaustion in order to boost anti‐tumour immunity. The discovery and development of the CRISPR/Cas9 technology offer a flexible and efficient gene‐editing capability in modulating various pathways that mediate NK cell exhaustion, and in arming NK cells with novel chimeric antigen receptors to specifically target tumour cells. Despite the high efficiency in its gene‐editing capability, difficulty in the delivery of the CRISPR/Cas9 system remains a major bottleneck for its therapeutic applications, particularly for NK cells. The current review discusses feasible approaches to deliver the CRISPR/Cas9 systems, as well as potential strategies in gene‐editing for NK cell immunotherapy for cancers.