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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/4368

Title: Therapeutic Anti-KIR Antibody of 1–7F9 Attenuates the Antitumor Effects of Expanded and Activated Human Primary Natural Killer Cells on In Vitro Glioblastoma-like Cells and Orthotopic Tumors Derived Therefrom
Other Titles: 治療用抗KIR抗体1-7F9は活性化ヒトNK細胞の膠芽腫細胞株、およびそれに由来する膠芽腫マウスモデルに対する抗腫瘍効果を抑制する
Authors: Maeoka, Ryosuke
Nakazawa, Tsutomu
Matsuda, Ryosuke
Morimoto, Takayuki
Shida, Yoichi
Yamada, Shuichi
Nishimura, Fumihiko
Nakamura, Mitsutoshi
Nakagawa, Ichiro
Park, Young-Soo
Tsujimura, Takahiro
Nakase, Hiroyuki
Keywords: NK cell
glioblastoma
immunotherapy
KIR
GiNKs
Issue Date: Sep-2023
Publisher: MDPI
Citation: International Journal of Molecular Sciences. 2023 Sep, vol.24, no.18, article no.14183
Abstract: Glioblastoma (GBM) is the leading malignant intracranial tumor, where prognosis for which has remained extremely poor for two decades. Immunotherapy has recently drawn attention as a cancer treatment, including for GBM. Natural killer (NK) cells are immune cells that attack cancer cells directly and produce antitumor immunity-related cytokines. The adoptive transfer of expanded and activated NK cells is expected to be a promising GBM immunotherapy. We previously established an efficient expansion method that produced highly purified, activated primary human NK cells, which we designated genuine induced NK cells (GiNKs). The GiNKs demonstrated antitumor effects in vitro and in vivo, which were less affected by blockade of the inhibitory checkpoint receptor programmed death 1 (PD-1). In the present study, we assessed the antitumor effects of GiNKs, both alone and combined with an antibody targeting killer Ig-like receptor 2DLs (KIR2DL1 and DL2/3, both inhibitory checkpoint receptors of NK cells) in vitro and in vivo with U87MG GBM-like cells and the T98G GBM cell line. Impedance-based real-time cell growth assays and apoptosis detection assays revealed that the GiNKs exhibited growth inhibitory effects on U87MG and T98G cells by inducing apoptosis. KIR2DL1 blockade attenuated the growth inhibition of the cell lines in vitro. The intracranial administration of GiNKs prolonged the overall survival of the U87MG-derived orthotopic xenograft brain tumor model. The KIR2DL1 blockade did not enhance the antitumor effects; rather, it attenuated it in the same manner as in the in vitro experiment. GiNK immunotherapy directly administered to the brain could be a promising immunotherapeutic alternative for patients with GBM. Furthermore, KIR2DL1 blockade appeared to require caution when used concomitantly with GiNKs.
Description: 権利情報:© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
URI: http://hdl.handle.net/10564/4368
ISSN: 1661-6596
DOI: https://doi.org/10.3390/ijms241814183
Academic Degrees and number: 24601甲第917号
Degree-granting date: 2024-03-14
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2023年度

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