决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Chimeric Antigen Receptor-T Cell Therapy Decreases Distant Metastasis and Inhibits Local Recurrence Post-surgery in Mice.
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。
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。
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.
MEMBER ACCOUNT
登录成功会直接打开下一页。