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[现成的同种异体嵌合抗原受体自然杀伤细胞疗法的现状与未来前景]

[Current state and future prospects of off-the-shelf allogeneic CAR NK therapy].

作者信息

Imai Chihaya

机构信息

Department of Pediatrics, Faculty of Medicine, University of Toyama.

出版信息

Rinsho Ketsueki. 2024;65(7):668-675. doi: 10.11406/rinketsu.65.668.

Abstract

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.

摘要

靶向CD19的嵌合抗原受体转导的自体T(CAR-T)细胞疗法彻底改变了CD19阳性血液肿瘤的治疗方式,包括急性淋巴细胞白血病和大B细胞淋巴瘤。然而,尽管缓解率很高,但许多问题已变得明显,如成本极高、物流复杂、速度不足以及生产失败等。解决这些问题的一个办法是使用同种异体细胞作为进行CAR基因改造的效应细胞。同种异体或“现成可用”的表达CAR的免疫效应细胞包括:1)使用健康成年供体T细胞生成的经过基因组编辑、T细胞受体(TCR)基因敲除的CAR-T细胞;2)诱导多能干细胞衍生的CAR-T细胞;3)CAR-NK细胞。NK细胞因体外扩增能力差和对基因改造的敏感性低而声名狼藉。在本文中,我将回顾同种异体CAR细胞疗法的现状和未来前景,特别提及CAR-NK细胞。

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