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CAR-T 细胞治疗减少小鼠远处转移并抑制术后局部复发

英文原题:Chimeric Antigen Receptor-T Cell Therapy Decreases Distant Metastasis and Inhibits Local Recurrence Post-surgery in Mice.

PubMed 2023/12/01(内容时间) Hum Gene Ther Q1 · IF 4.6(JCR 2025)

研究概要

远处转移和原发肿瘤复发是癌症患者手术治疗成功的两大主要障碍。

中文摘要

远处转移和原发肿瘤复发是影响癌症患者手术治疗成功的两大难题。循环肿瘤细胞(CTC)和手术切除不完全分别是远处转移和局部复发的主要原因。靶向残留癌细胞和CTC的嵌合抗原受体(CAR)修饰T细胞有望抑制原发肿瘤复发并减少转移,但此前缺乏实验依据。本研究在免疫功能完整的小鼠中建立手术诱导肿瘤转移模型,评估CAR-T细胞预防转移及局部复发的效果。研究观察到,皮下肿瘤切除会导致大量CTC进入循环。肿瘤切除后给予EpCAM特异性CAR-T,可有效清除CTC。与手术后输注模拟T细胞的小鼠相比,这些小鼠肺转移更少、生存时间更长。此外,术后给予EpCAM-CAR-T还明显抑制了手术部位的局部复发。本研究显示,对癌症患者而言,术后CAR-T细胞治疗可作为辅助治疗,以预防肿瘤转移并抑制原发肿瘤复发。

展开英文摘要原文

Distant metastasis and primary tumor relapse are the two main hurdles to the success of surgical treatment for cancer patients. Circulating tumor cells (CTCs) and incomplete surgical resection are the primary cause of distant metastasis and local recurrence of tumors, respectively. Chimeric antigen receptor (CAR)-modified T cells target residual carcinomas and CTCs hold the potential to inhibit primary recurrence and reduce tumor metastasis, but the experimental evidence is lacking. Here, we developed a surgery-induced tumor metastasis model in immunocompetent mice to investigate the efficacy of CAR-T cells therapy in preventing metastasis and local recurrence. We observed that subcutaneous tumor resection has induced a large number of CTCs intravasated into circulation. EpCAM-specific CAR-T was effective in clearing CTCs following surgical removal of the tumor. This resulted in less pulmonary metastasis and longer survival in mice when compared to mice treated with surgery followed by Mock-T cells infusion. In addition, the local relapse was obviously inhibited at the surgical site followed by EpCAM-CAR-T cell treatment. This study demonstrated that CAR-T cell therapy can be an adjuvant treatment following surgery to prevent tumor metastasis and inhibit primary tumor relapse for cancer patients.

论文信息

作者
Li D、Jiang L、Zhou W、Huang Y、Yang Y、Li J、Yang J、Wang F
单位
Department of Biotherapy, The State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.China
文献类型
非美国政府资助研究
期刊
Human gene therapy2023 Dec
原文标识
PubMed 37917093 · DOI 10.1089/hum.2023.144