CAR-T细胞治疗可减少小鼠的远处转移并抑制术后局部复发。

IF 3.9 3区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Dan Li, Lin Jiang, Weilin Zhou, Yong Huang, Yuening Yang, Jing Li, Jinrong Yang, Fengling Wang, Jiaqian Li, Yalan Zhang, Feiyang Yan, Haozhan Gao, Xianling Guo, Qing Xu, Shisheng Tan, Yu-Quan Wei, Wei Wang
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引用次数: 0

摘要

远处转移和原发性肿瘤复发是癌症患者手术治疗成功的两大障碍。循环肿瘤细胞(CTCs)和不完全手术切除分别是肿瘤远处转移和复发的主要原因。嵌合抗原受体(CAR)修饰的T细胞靶向残留癌,CTC具有抑制原发性复发和减少肿瘤转移的潜力,但缺乏实验证据。在这里,我们在免疫活性小鼠中开发了一种手术诱导的肿瘤转移模型,以研究CAR-T细胞治疗在预防转移和局部复发方面的疗效。我们观察到皮下肿瘤切除诱导了大量CTC进入循环。EpCAM特异性CAR-T在肿瘤手术切除后清除CTC方面是有效的。与用Mock-T细胞进行手术治疗的小鼠相比,这导致小鼠的肺转移更少,存活时间更长。此外,EpCAM-CAR-T细胞治疗后,手术部位的局部复发得到明显抑制。这项研究表明,CAR-T细胞治疗可以作为癌症患者手术后的辅助治疗,以预防肿瘤转移和抑制原发性肿瘤复发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chimeric Antigen Receptor-T Cell Therapy Decreases Distant Metastasis and Inhibits Local Recurrence Post-surgery in Mice.

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.

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来源期刊
Human gene therapy
Human gene therapy 医学-生物工程与应用微生物
CiteScore
6.50
自引率
4.80%
发文量
131
审稿时长
4-8 weeks
期刊介绍: Human Gene Therapy is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes in-depth coverage of DNA, RNA, and cell therapies by delivering the latest breakthroughs in research and technologies. Human Gene Therapy provides a central forum for scientific and clinical information, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases.
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