论文
论文题目: CRISPR-Cas9-Mediated Multiplex Gene Editing in CAR-T Cells
论文题目英文:
作者: 刘晓娟①,#张永平①,程晨①,#Albert W Cheng,张兴颖,Na Li,#Chang-Qing Xia,#Xiao-Fei Wei,刘相,王皓毅*
论文出处:
年: 2016
卷:
期: DOI: 10.1038/cr.2016.142
页:
联系作者: 王皓毅
发表期刊: Cell Research
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第一作者所在部门:
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论文连接 http://www.nature.com/cr/journal/vaop/ncurrent/full/cr2016142a.html
影响因子:
摘要: Chimeric antigen receptor (CAR) T cell therapy is a promising approach to treat cancer, such as B-cell malignancy1. However, the current standard treatment requires autologous adoptive cell transfer, which is expensive and time-consuming. For newborn and elder patients, it is often difficult to obtain enough T cells with good quality to generate patient-specific CAR-T cells. To make CAR-T therapy more accessible, it is highly desirable to develop an allogeneic adoptive transfer strategy, in which universal CAR-T cells derived from T cells from healthy donors can be applied to treat multiple patients. For this strategy to work, the αβ T-cell receptor (TCR) on allogeneic CAR-T cells needs to be eliminated to avoid graft-versus-host-disease (GVHD), and human leukocyte antigens class I (HLA-Is) on CAR-T cells need to be removed to minimize their immunogenicity. Previous studies have shown that mutation in TCRα subunit constant (TRAC) leads to loss of αβ TCR on T-cell surface2, and beta-2 microglobulin (B2M) is essential for cell-surface expression of HLA-I heterodimers3. Thus, we attempted to target TRAC and B2M genes in CAR-T cells. Considering blocking programmed death-1 (PD-1) signaling can effectively treat cancers via reversing immunosuppression, we also targeted PD-1 in CAR-T cells to render them nonresponsive to PD-1 signaling4...
英文摘要:
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