Dual-antigen targeted iPSC-derived chimeric antigen receptor-T cell therapy for refractory lymphoma

Sakiko Harada, Miki Ando*, Jun Ando, Midori Ishii, Tomoyuki Yamaguchi, Satoshi Yamazaki, Tokuko Toyota, Kazuo Ohara, Manami Ohtaka, Mahito Nakanishi, Chansu Shin, Yasunori Ota, Kazutaka Nakashima, Koichi Ohshima, Chihaya Imai, Yozo Nakazawa, Hiromitsu Nakauchi*, Norio Komatsu

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

30 被引用数 (Scopus)

抄録

We generated dual-antigen receptor (DR) T cells from induced pluripotent stem cells (iPSCs) to mitigate tumor antigen escape. These cells were engineered to express a chimeric antigen receptor (CAR) for the antigen cell surface latent membrane protein 1 (LMP1; LMP1-CAR) and a T cell receptor directed to cell surface latent membrane protein 2 (LMP2), in association with human leucocyte antigen A24, to treat therapy-refractory Epstein-Barr virus-associated lymphomas. We introduced LMP1-CAR into iPSCs derived from LMP2-specific cytotoxic T lymphocytes (CTLs) to generate rejuvenated CTLs (rejTs) active against LMP1 and LMP2, or DRrejTs. All DRrejT-treated mice survived >100 days. Furthermore, DRrejTs rejected follow-up inocula of lymphoma cells, demonstrating that DRrejTs persisted long-term. We also demonstrated that DRrejTs targeting CD19 and LMP2 antigens exhibited a robust tumor suppressive effect and conferred a clear survival advantage. Co-operative antitumor effect and in vivo persistence, with unlimited availability of DRrejT therapy, will provide powerful and sustainable T cell immunotherapy.

本文言語英語
ページ(範囲)534-549
ページ数16
ジャーナルMolecular Therapy
30
2
DOI
出版ステータス出版済み - 2022/02/02

ASJC Scopus 主題領域

  • 分子医療
  • 分子生物学
  • 遺伝学
  • 薬理学
  • 創薬

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