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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors

  • Kim, Nayoung (Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Dong-Hee (Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Choi, Woo Seon (Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Yi, Eunbi (Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, HyoJeong (Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Jung Min (Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jin, Hyung-Seung (Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Hun Sik (Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2020.09.29
  • Accepted : 2020.12.03
  • Published : 2021.01.31
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Abstract

Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.

Keywords

Acknowledgement

This study was supported by a grant from the National Research Foundation of Korea (2019R1A2C2006475) and an MRC grant (2018R1A5A2020732) funded by the Korean government (MSIT).

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