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Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors
Nayoung Kim2,# (Research Professor), Dong-Hee Lee2,# (Graduate student), Woo Seon Choi1,# (Research worker), Eunbi Yi1 (Post-Doc), HyoJeong Kim1 (Research worker), Jung Min Kim1 (Graduate student), Hyung-Seung Jin2 (Research Professor), Hun Sik Kim 1,* (Associate Professor)
1Biomedical Sciences and 2Convergence Medicine, University of Ulsan College of Medicine
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.
Abstract, Accepted Manuscript(in press) [Submitted on September 29, 2020, Accepted on December 3, 2020]
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