期刊
LIFE SCIENCES
卷 316, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2023.121409
关键词
CRISPR; Cas9; CAR -T cell therapy; Cytokine release syndrome; TGF-? resistance; Multiplex genome editing; Allogeneic CAR -T cell; Limitations; Next-generation CAR -T cells; Tumor; Immunotherapy
The innovative CRISPR/Cas9 technology has the potential to overcome the challenges in CAR-T cell therapy for malignancies and improve antitumor efficacy, providing opportunities for novel cancer immunotherapies.
Chimeric antigen receptor (CAR) T therapy has shown remarkable success in discovering novel CAR-T cell products for treating malignancies. Despite of successful results from clinical trials, CAR-T cell therapy is inef-fective for long-term disease progression. Numerous challenges of CAR-T cell immunotherapy such as cell dysfunction, cytokine-related toxicities, TGF-beta resistance, GvHD risks, antigen escape, restricted trafficking, and tumor cell infiltration still exist that hamper the safety and efficacy of CAR-T cells for malignancies. The accu-mulated data revealed that these challenges could be overcome with the advanced CRISPR genome editing technology, which is the most promising tool to knockout TRAC and HLA genes, inhibiting the effects of dominant negative receptors (PD-1, TGF-beta, and B2M), lowering the risks of cytokine release syndrome (CRS), and regulating CAR-T cell function in the tumor microenvironment (TME). CRISPR technology employs DSB-free genome editing methods that robustly allow efficient and controllable genetic modification. The present re-view explored the innovative aspects of CRISPR/Cas9 technology for developing next-generation/universal allogeneic CAR-T cells. The present manuscript addressed the ongoing status of clinical trials of CRISPR/Cas9-engineered CAR-T cells against cancer and pointed out the off-target effects associated with CRISPR/Cas9 genome editing. It is concluded that CAR-T cells modified by CRISPR/Cas9 significantly improved antitumor efficacy in a cost-effective manner that provides opportunities for novel cancer immunotherapies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据