Novel application of radotinib for the treatment of solid tumors via natural killer cell activation

Kyung Eun Kim, Sunyoung Park, Soyoung Cheon, Dong Yeon Kim, Dae Jin Cho, Jeong Min Park, Dae Young Hur, Hyun Jeong Park, Dae Ho Cho

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Abstract

Radotinib (SupectTM) was developed to treat chronic myeloid leukemia (CML) as a BCR-ABL1 tyrosine kinase inhibitor (TKI). Other TKIs, including imatinib and nilotinib, were also developed for treatment of CML, and recent studies were increasing about the therapeutic effects of other TKIs on solid tumors. However, the effect of radotinib on solid tumors has not yet been investigated. In this study, radotinib killed CML cell line K562 directly; however, radotinib did not enhance NK cell cytotoxicity against K562 cells. Because K562 is known as a Fas-negative cell line, we investigated whether radotinib could regulate cell cytotoxicity against various Fas-expressing solid cancer cell lines. Radotinib dramatically increased NK cell cytotoxicity against various Fas-expressing solid cancer cells, including lung, breast, and melanoma cells. Additionally, the efficiency of radotinib-enhanced cytotoxicity was lower in Fas siRNA-transfected cells than in negative controls, suggesting that Fas signaling might be involved in the radotinib-enhanced NK cell cytotoxicity. This study provides the first evidence that radotinib could be used as an effective and strong therapeutic to treat solid tumors via upregulation of NK cell cytotoxicity, suggesting that radotinib has indirect killing mechanisms via upregulation of antitumor innate immune responses as well as direct killing activities for CML cells.

Original languageEnglish
Article number9580561
JournalJournal of Immunology Research
Volume2018
DOIs
Publication statusPublished - 2018 Jan 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kim, K. E., Park, S., Cheon, S., Kim, D. Y., Cho, D. J., Park, J. M., Hur, D. Y., Park, H. J., & Cho, D. H. (2018). Novel application of radotinib for the treatment of solid tumors via natural killer cell activation. Journal of Immunology Research, 2018, [9580561]. https://doi.org/10.1155/2018/9580561