| Title: |
CRISPR-Cas9-Mediated Multiplex Gene Editing in CAR-T Cells |
| Author: |
Xiaojuan Liu, Yongping Zhang, Chen Cheng, Albert W Cheng, Xingying Zhang, Na Li, Changqing Xia, Xiaofei Wei, Xiang Liu, Haoyi Wang |
| Abstract: |
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. ... |
| Corresponding author: |
Haoyi Wang |
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| PubYear: |
2016 |
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| Issue: |
DOI: 10.1038/cr.2016.142 |
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| Journal: |
Cell Research |
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