Kim Ji Hwan, Kim Hyori, Lee A-Neum, Park Hyung Bae, Choi Kyungho
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea.
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
Immune Netw. 2024 Dec 24;24(6):e43. doi: 10.4110/in.2024.24.e43. eCollection 2024 Dec.
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 expanded T cells, thereby effectively depleting residual TCR-positive T cells during TCR-deleted CAR-T cell generation and ultimately preventing xenogeneic GVHD . Thus, monovalent anti-CD3 treatment during allogeneic CAR-T cell manufacturing would be an efficient method to prevent GVHD.
嵌合抗原受体转导的T（CAR-T）细胞疗法是一种针对晚期血液系统肿瘤的有效细胞疗法。然而，自体T细胞的使用限制了其及时和广泛的产生。同种异体CAR-T细胞疗法作为一种即用型治疗方法可能是一个很好的选择。移植物抗宿主病（GVHD）是同种异体CAR-T细胞面临的一个障碍，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（scFv），而非完整的IgG，可诱导扩增的T细胞凋亡，从而在删除TCR的CAR-T细胞生成过程中有效耗尽残留的TCR阳性T细胞，并最终预防异种GVHD。因此，在同种异体CAR-T细胞制造过程中进行单价抗CD3治疗将是预防GVHD的一种有效方法。
