CAR-T 细胞疗法可减少小鼠的远处转移并抑制术后局部复发。
CAR-T Cell Therapy Decreases Distant Metastasis and Inhibits Local Recurrence Post-surgery in Mice.
发表日期:2023 Nov 02
作者:
Dan Li, Lin Jiang, Weiling Zhou, Yong Huang, Yuening Yang, Jing Li, Jinrong Yang, Fengling Wang, Jiaqian Li, Yalan Zhang, Feiyang Yan, Haozhan Gao, Xianling Guo, Qing Xv, Shisheng Tan, Yu-Quan Wei, Wei Wang
来源:
Experimental Hematology & Oncology
摘要:
远处转移和原发肿瘤复发是癌症患者手术治疗成功的两个主要障碍。循环肿瘤细胞(CTC)和手术切除不彻底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,我们在免疫功能正常的小鼠中开发了手术诱导的肿瘤转移模型,以研究 CAR-T 细胞疗法在预防转移和局部复发方面的功效。我们观察到皮下肿瘤切除术诱导大量CTCs进入循环。 EpCAM 特异性 CAR-T 在手术切除肿瘤后可有效清除 CTC。与先接受手术后再接受模拟 T 细胞治疗的小鼠相比,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明显受到抑制。这项研究表明,CAR-T细胞疗法可以作为癌症患者手术后的辅助治疗,以预防肿瘤转移并抑制原发性肿瘤复发。
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 recurrence of tumors respectively. Chimeric antigen receptor (CAR)-modified T cells targets 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. 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.