Ex vivo generation of highly purified and activated natural killer cells from human peripheral blood

Satoru Saito, Yui Harada, Yosuke Morodomi, Mitsuho Onimaru, Kumi Yoshida, Ryoichi Kyuragi, Hisahiro Matsubara, Yoshikazu Yonemitsu

研究成果: ジャーナルへの寄稿学術誌査読

5 被引用数 (Scopus)

抄録

Adoptive immunotherapy using natural killer (NK) cells has been a promising treatment for intractable malignancies; however, there remain a number of difficulties with respect to the shortage and limited anticancer potency of the effector cells. We here established a simple feeder-free method to generate purified (>90%) and highly activated NK cells from human peripheral blood-derived mononuclear cells (PBMCs). Among the several parameters, we found that CD3 depletion, high-dose interleukin (IL)-2, and use of a specific culture medium were sufficient to obtain highly purified, expanded (∼200-fold) and activated CD3-/CD56+ NK cells from PBMCs, which we designated zenithal-NK (Z-NK) cells. Almost all Z-NK cells expressed the lymphocyte-activated marker CD69 and showed dramatically high expression of activation receptors (i.e., NKG2D), interferon-γ, perforin, and granzyme B. Importantly, only 2 hours of reaction at an effector/target ratio of 1:1 was sufficient to kill almost all K562 cells, and the antitumor activity was also replicated in tumor-bearing mice in vivo. Cytolysis was specific for various tumor cells, but not for normal cells, irrespective of MHC class I expression. These findings strongly indicate that Z-NK cells are purified, expanded, and near-fully activated human NK cells and warrant further investigation in a clinical setting.

本文言語英語
ページ(範囲)241-252
ページ数12
ジャーナルHuman Gene Therapy Methods
24
4
DOI
出版ステータス出版済み - 8月 1 2013

!!!All Science Journal Classification (ASJC) codes

  • 分子医療
  • 応用微生物学とバイオテクノロジー
  • 遺伝学
  • 薬理学
  • 遺伝学(臨床)

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