单价抗cd3抗体有效消除tcr缺失的异体CAR-T细胞中tcr阳性部分以预防GVHD

IF 4.3 4区 医学 Q2 IMMUNOLOGY
Immune Network Pub Date : 2024-12-24 eCollection Date: 2024-12-01 DOI:10.4110/in.2024.24.e43
Ji Hwan Kim, Hyori Kim, A-Neum Lee, Hyung Bae Park, Kyungho Choi
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引用次数: 0

摘要

嵌合抗原受体转导T细胞疗法是一种有效的治疗晚期血液肿瘤的细胞疗法。然而,自体T细胞的使用限制了其及时和普遍的产生。同种异体CAR-T细胞疗法可能是一种现成的治疗方法。移植物抗宿主病(GVHD)是同种异体CAR-T细胞的障碍,但可以通过基因组编辑删除TCR来预防。然而,剩余的tcr阳性细胞必须通过昂贵的大规模磁性细胞分离来消除。因此,需要一种去除tcr阳性细胞的替代方法。在本研究中,我们发现单价抗cd3抗体如Fab和单链可变片段(single-chain variable fragment, scFv),而不是完整的IgG,可以诱导体外扩增的T细胞凋亡,从而在tcr缺失的CAR-T细胞生成过程中有效地消耗残余的tcr阳性T细胞,最终在体内预防异种性GVHD。因此,在同种异体CAR-T细胞制造过程中,单价抗cd3治疗将是预防GVHD的有效方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Monovalent Anti-CD3 Antibodies Effectively Eliminate the TCR-Positive Fraction of TCR-Deleted Allogeneic CAR-T Cells to Prevent GVHD.

Chimeric antigen receptor-transduced T (CAR-T) cell therapy is an effective cell therapy against advanced hematological tumors. However, the use of autologous T cells limits its timely and universal generation. Allogeneic CAR-T cell therapy may be a good alternative as a ready-to-use therapeutic. Graft-versus-host disease (GVHD) is an obstacle for allogeneic CAR-T cells, but can be prevented by TCR deletion through genome editing. However, the remaining TCR-positive cells must be eliminated by costly, large-scale magnetic cell separation. Therefore, an alternative method for removing TCR-positive cells is needed. In this study, we found that monovalent anti-CD3 Abs such as Fab and single-chain variable fragment (scFv), but not whole IgG, induce apoptosis of in vitro expanded T cells, thereby effectively depleting residual TCR-positive T cells during TCR-deleted CAR-T cell generation and ultimately preventing xenogeneic GVHD in vivo. Thus, monovalent anti-CD3 treatment during allogeneic CAR-T cell manufacturing would be an efficient method to prevent GVHD.

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来源期刊
Immune Network
Immune Network Immunology and Microbiology-Immunology
CiteScore
2.90
自引率
3.30%
发文量
36
期刊介绍: Immune Network publishes novel findings in basic and clinical immunology and aims to provide a medium through which researchers in various fields of immunology can share and connect. The journal focuses on advances and insights into the regulation of the immune system and the immunological mechanisms of various diseases. Research that provides integrated insights into translational immunology is given preference for publication. All submissions are evaluated based on originality, quality, clarity, and brevity
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