[现成的同种异体 CAR NK 疗法的现状和未来前景]。

Chihaya Imai
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引用次数: 0

摘要

靶向 CD19 的嵌合抗原受体转导自体 T(CAR-T)细胞疗法彻底改变了 CD19 阳性血液肿瘤(包括急性淋巴细胞白血病和大 B 细胞淋巴瘤)的治疗方法。然而,尽管反应率很高,但成本过高、物流复杂、速度不够快、制造失败等诸多问题也已显现。解决这些问题的方法之一是使用异体细胞作为效应细胞,用 CAR 进行基因修饰。异体或 "现成的 "CAR表达免疫效应细胞包括:1)基因组编辑、T细胞受体(TCR)基因删除的CAR-T细胞,使用健康的成人供体T细胞生成;2)诱导多能干细胞衍生的CAR-T细胞;3)CAR NK细胞。NK 细胞因其体内外扩增能力差和基因修饰敏感性低而臭名昭著。在本文中,我将回顾异基因CAR细胞疗法的现状和未来前景,特别是CAR NK细胞。
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[Current state and future prospects of off-the-shelf allogeneic CAR NK therapy].

Chimeric antigen receptor-transduced autologous T (CAR-T) cell therapy targeting CD19 has revolutionized the treatment of CD19-positive hematological tumors, including acute lymphoblastic leukemia and large B-cell lymphoma. However, despite the high response rate, many problems such as exceedingly high cost, complex logistics, insufficient speed, and manufacturing failures have become apparent. One solution for these problems is to use an allogeneic cell as an effector cell for genetic modification with CAR. Allogeneic, or "off-the-shelf", CAR-expressing immune-effector cells include 1) genome-edited, T-cell receptor (TCR) gene-deleted CAR-T cells generated using healthy adult donor T cells, 2) induced pluripotent stem cell-derived CAR-T cells, and 3) CAR NK cells. NK cells are notorious for their poor ex-vivo expansion and low susceptibility to genetic modification. In this article, I will review the current state and future prospects of allogeneic CAR cell therapies, with special reference to CAR NK cells.

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