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Research ArticleExperimental Studies

Novel Human NK Cell Line Carrying CAR Targeting EGFRvIII Induces Antitumor Effects in Glioblastoma Cells

TOSHIHARU MURAKAMI, TSUTOMU NAKAZAWA, ATSUSHI NATSUME, FUMIHIKO NISHIMURA, MITSUTOSHI NAKAMURA, RYOSUKE MATSUDA, KOJI OMOTO, YOSHITAKA TANAKA, YOUICHI SHIDA, YOUNG-SOO PARK, YASUSHI MOTOYAMA, ICHIRO NAKAGAWA, SHUICHI YAMADA, KENTARO TAMURA, YASUHIRO TAKESHIMA, YOSHIAKI TAKAMURA, TOSHIHIKO WAKABAYASHI and HIROYUKI NAKASE
Anticancer Research September 2018, 38 (9) 5049-5056; DOI: https://doi.org/10.21873/anticanres.12824
TOSHIHARU MURAKAMI
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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TSUTOMU NAKAZAWA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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ATSUSHI NATSUME
2Department of Neurosurgery, Nagoya University, Graduate School of Medicine, Nagoya, Japan
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FUMIHIKO NISHIMURA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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  • For correspondence: fnishi@naramed-u.ac.jp
MITSUTOSHI NAKAMURA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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RYOSUKE MATSUDA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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KOJI OMOTO
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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YOSHITAKA TANAKA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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YOUICHI SHIDA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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YOUNG-SOO PARK
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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YASUSHI MOTOYAMA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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ICHIRO NAKAGAWA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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SHUICHI YAMADA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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KENTARO TAMURA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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YASUHIRO TAKESHIMA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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YOSHIAKI TAKAMURA
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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TOSHIHIKO WAKABAYASHI
2Department of Neurosurgery, Nagoya University, Graduate School of Medicine, Nagoya, Japan
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HIROYUKI NAKASE
1Department of Neurosurgery, Nara Medical University, Kashihara, Japan
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Abstract

Background/Aim: Natural killer (NK) cells are considered potential antitumor effector cells. The aim of this study was to establish a novel type of a chimeric antigen receptor (CAR) NK cell line (CAR-KHYG-1) specific for epidermal growth factor receptor variant III (EGFRvIII)-expressing tumors and investigate the anti-tumor activity of EGFRvIII-specific-CAR-KHYG-1 (EvCAR-KHYG-1). Materials and Methods: EvCAR-KHYG-1 was established by self-inactivated lentiviral-based transduction of the EvCAR gene and magnetic bead-based purification of EvCAR-expressing NK cells. The anti-tumor effects of EvCAR-KHYG-1 were evaluated using growth inhibition and apoptosis detection assays in glioblastoma (GBM) cell lines (EGFRvIII-expressing and non-expressing U87MG). Results: The findings demonstrated that EvCAR-KHYG-1 inhibited GBM cell-growth via apoptosis in an EGFRvIII-expressing specific manner. Conclusion: This is the first study to establish a CAR NK cell line based on the human NK cell line KHYG-1. Therapy with EvCAR-KHYG-1 may be an effective treatment option for GBM patients.

  • Chimeric antigen receptor
  • natural killer cells
  • glioblastoma
  • epidermal growth factor receptor variant III
  • Received July 21, 2018.
  • Revision received August 2, 2018.
  • Accepted August 6, 2018.
  • Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
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Anticancer Research: 38 (9)
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September 2018
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Novel Human NK Cell Line Carrying CAR Targeting EGFRvIII Induces Antitumor Effects in Glioblastoma Cells
TOSHIHARU MURAKAMI, TSUTOMU NAKAZAWA, ATSUSHI NATSUME, FUMIHIKO NISHIMURA, MITSUTOSHI NAKAMURA, RYOSUKE MATSUDA, KOJI OMOTO, YOSHITAKA TANAKA, YOUICHI SHIDA, YOUNG-SOO PARK, YASUSHI MOTOYAMA, ICHIRO NAKAGAWA, SHUICHI YAMADA, KENTARO TAMURA, YASUHIRO TAKESHIMA, YOSHIAKI TAKAMURA, TOSHIHIKO WAKABAYASHI, HIROYUKI NAKASE
Anticancer Research Sep 2018, 38 (9) 5049-5056; DOI: 10.21873/anticanres.12824

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Novel Human NK Cell Line Carrying CAR Targeting EGFRvIII Induces Antitumor Effects in Glioblastoma Cells
TOSHIHARU MURAKAMI, TSUTOMU NAKAZAWA, ATSUSHI NATSUME, FUMIHIKO NISHIMURA, MITSUTOSHI NAKAMURA, RYOSUKE MATSUDA, KOJI OMOTO, YOSHITAKA TANAKA, YOUICHI SHIDA, YOUNG-SOO PARK, YASUSHI MOTOYAMA, ICHIRO NAKAGAWA, SHUICHI YAMADA, KENTARO TAMURA, YASUHIRO TAKESHIMA, YOSHIAKI TAKAMURA, TOSHIHIKO WAKABAYASHI, HIROYUKI NAKASE
Anticancer Research Sep 2018, 38 (9) 5049-5056; DOI: 10.21873/anticanres.12824
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Keywords

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