CXCL9 修饰的 CAR T 细胞改善免疫细胞浸润和抗肿瘤疗效。
CXCL9-modified CAR T cells improve immune cell infiltration and antitumor efficacy.
机构信息
Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, 450052, Henan, China.
出版信息
Cancer Immunol Immunother. 2022 Nov;71(11):2663-2675. doi: 10.1007/s00262-022-03193-6. Epub 2022 Mar 29.
Chimeric antigen receptor (CAR) T cells remain unsatisfactory in treating solid tumors. The frequency of tumor-infiltrating T cells is closely related to the good prognosis of patients. Augmenting T cell accumulation in the tumor microenvironment is essential for tumor clearance. To overcome insufficient immune cell infiltration, innovative CAR designs need to be developed immediately. CXCL9 plays a pivotal role in regulating T cell migration and inhibiting tumor angiogenesis. Therefore, we engineered CAR T cells expressing CXCL9 (CART-CXCL9). The addition of CXCL9 enhanced cytokine secretion and cytotoxicity of CAR T cells and endowed CAR T cells with the ability to recruit activated T cells and antiangiogenic effect. In tumor-bearing mice, CART-CXCL9 cells attracted more T cell trafficking to the tumor site and inhibited angiogenesis than conventional CAR T cells. Additionally, CART-CXCL9 cell therapy slowed tumor growth and prolonged mouse survival, displaying superior antitumor activity. Briefly, modifying CAR T cells to express CXCL9 could effectively improve CAR T cell efficacy against solid tumors.
嵌合抗原受体 (CAR) T 细胞在治疗实体瘤方面仍不尽人意。肿瘤浸润 T 细胞的频率与患者的良好预后密切相关。增强肿瘤微环境中 T 细胞的积累对于清除肿瘤至关重要。为了克服免疫细胞浸润不足的问题，需要立即开发创新的 CAR 设计。CXCL9 在调节 T 细胞迁移和抑制肿瘤血管生成方面发挥着关键作用。因此，我们构建了表达 CXCL9 的 CAR T 细胞（CART-CXCL9）。添加 CXCL9 增强了 CAR T 细胞的细胞因子分泌和细胞毒性，并赋予 CAR T 细胞招募激活的 T 细胞和抗血管生成的能力。在荷瘤小鼠中，与传统的 CAR T 细胞相比，CART-CXCL9 细胞更能吸引更多的 T 细胞向肿瘤部位迁移并抑制血管生成。此外，CART-CXCL9 细胞治疗可减缓肿瘤生长并延长小鼠存活时间，显示出优异的抗肿瘤活性。简而言之，修饰 CAR T 细胞以表达 CXCL9 可以有效提高 CAR T 细胞对实体瘤的疗效。
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