Generation of chimeric antigen receptor-macrophages by using human induced pluripotent stem cells.

IF 2.5 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kenji Kitajima, Takahiko Hara
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引用次数: 0

Abstract

Cancer immunotherapy using chimeric antigen receptor (CAR) cells shows high therapeutic efficacy against several types of leukemia. Among acute lymphoblastic leukemias (ALLs), B cell-derived ALL can be cured by CAR-expressing T cells (CAR-Ts); however, CAR-T cells cannot be simply applied for T cell-derived ALL (T-ALL) because antigens expressed by T-ALL cells, but not by CAR-T cells, have not yet been identified. To apply CAR-T therapy for T-ALL, gene editing of CAR-T cells is required to avoid attacking CAR-T cells themselves. Alternatively, CAR-expressing macrophages (CAR-Ms) have proven to be effective against various cancers, suggesting that CAR-Ms may also be effective against T-ALL. Recently, we developed an efficient differentiation induction system to generate a large number of macrophages from human induced pluripotent stem cells (iPSCs). Here, we asked whether these human iPSC-derived macrophages (iPS-MACs) can be used to develop and evaluate CAR-based immunotherapy against T-ALLs. When non-transduced iPS-MACs were co-cultured with human T-ALL-derived cells, the iPS-MACs appeared to phagocytose parts of T-ALL cells; this method of phagocytosis operated mainly through incorporation of small, "bite-sized" vesicles derived from the T-ALL cells into iPS-MACs (similar to trogocytosis). By contrast, when CAR-expressing iPS-MACs were co-cultured with T-ALL cells, iPS-MACs engulfed the whole T-ALL cell. Thus, our differentiation induction system may be a promising tool for building up CAR-M therapy for T-ALLs.

利用人类诱导多能干细胞生成嵌合抗原受体-巨噬细胞。
使用嵌合抗原受体(CAR)细胞的癌症免疫疗法对几种类型的白血病具有很高的疗效。在急性淋巴细胞白血病(ALL)中,B 细胞源性 ALL 可以通过 CAR 表达的 T 细胞(CAR-T)治愈;但是,CAR-T 细胞不能简单地应用于 T 细胞源性 ALL(T-ALL),因为 T-ALL 细胞表达的抗原尚未确定,而 CAR-T 细胞表达的抗原尚未确定。要将 CAR-T 疗法应用于 T-ALL 癌症,需要对 CAR-T 细胞进行基因编辑,以避免 CAR-T 细胞本身受到攻击。另外,CAR-表达巨噬细胞(CAR-Ms)已被证明对多种癌症有效,这表明CAR-Ms也可能对T-ALL有效。最近,我们开发了一种高效的分化诱导系统,可从人类诱导多能干细胞(iPSCs)中生成大量巨噬细胞。在此,我们想知道这些源自人类 iPSC 的巨噬细胞(iPS-MACs)是否可用于开发和评估针对 T-ALL 的基于 CAR 的免疫疗法。当未转导的 iPS-MACs 与人类 T-ALL 衍生细胞共同培养时,iPS-MACs 似乎能吞噬部分 T-ALL 细胞;这种吞噬方法主要是通过将 T-ALL 细胞衍生的 "一口大小 "的小囊泡纳入 iPS-MACs 来实现的(类似于蛙吞作用)。相比之下,当 CAR 表达的 iPS-MAC 与 T-ALL 细胞共培养时,iPS-MAC 会吞噬整个 T-ALL 细胞。因此,我们的分化诱导系统可能是建立T-ALL的CAR-M疗法的一种有前途的工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biochemical and biophysical research communications
Biochemical and biophysical research communications 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
1400
审稿时长
14 days
期刊介绍: Biochemical and Biophysical Research Communications is the premier international journal devoted to the very rapid dissemination of timely and significant experimental results in diverse fields of biological research. The development of the "Breakthroughs and Views" section brings the minireview format to the journal, and issues often contain collections of special interest manuscripts. BBRC is published weekly (52 issues/year).Research Areas now include: Biochemistry; biophysics; cell biology; developmental biology; immunology ; molecular biology; neurobiology; plant biology and proteomics
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