《生命科学》 2025, 37(9): 1173-1182

通用型CAR-T：基因编辑驱动“即用型”疗法新突破

张　婧 , 马　雯 , 王清路 , 周彩霞^*

山东体育学院研究生教育学院，济南 250102

摘　要：

嵌合抗原受体(chimeric antigen receptor T, CAR-T) 细胞疗法在B 细胞白血病等血液系统恶性肿瘤中取得了革命性突破，但仍面临细胞因子释放综合征(cytokine release syndrome, CRS)、移植物抗宿主病(graft-versus-host disease, GvHD) 和抗原逃逸等挑战。通用型CAR-T 细胞(universal CAR-T, UCART) 利用CRISPR/Cas9 等基因编辑技术改造异体T 细胞，实现“即用型”供应并降低免疫排斥风险。本文综述了UCAR-T 细胞的构建策略，包括筛选T 细胞来源、优化CAR 结构及CRISPR/Cas9 等基因编辑技术的应用；探讨了串联CAR 和开关型CAR-T 应对肿瘤异质性和抗原逃逸的策略。通过优化设计，UCAR-T 细胞有望为肿瘤免疫治疗提供安全高效的新路径。

通讯作者：周彩霞 , Email:zhoucaixia@sdpei.edu.cn

Universal CAR-T: gene editing drives new breakthroughs in “off-the-shelf” therapies

ZHANG Jing , MA Wen , WANG Qing-Lu , ZHOU Cai-Xia^*

Graduate Education College, Shandong Sport University, Jinan 250102, China

Abstract:

Chimeric antigen receptor T (CAR-T) cell therapy has achieved revolutionary breakthroughs in hematological malignancies such as B-cell leukemia, but still faces challenges such as cytokine release syndrome  (CRS), graft-versus-host disease (GvHD), and antigen escape. Universal CAR-T cells utilize gene editing techniques  such as CRISPR/Cas9 to modify allogeneic T cells, achieving "off-the-shelf" supply and reducing the risk of immune rejection. This article reviews the construction strategies of universal CAR-T cells, including screening T cell sources, optimizing CAR structures, and the application of gene editing technologies such as CRISPR/Cas9. Furthermore, we explore the issues of tandem CAR (TanCAR) and switchable CAR-T (sCAR-T) in addressing tumor heterogeneity and antigen escape. Through optimized design, universal CAR-T cells are expected to provide a safe and efficient new pathway for tumor immunotherapy.

Communication Author：ZHOU Cai-Xia , Email:zhoucaixia@sdpei.edu.cn