肿瘤细胞治疗研究
英文原题：Synergistic effect of chimeric antigen receptor modified with Bcl-2 on enhanced solid tumour targeting.
Synergistic effect of chimeric antigen receptor modified with Bcl-2 on enhanced solid tumour targeting.
我们的研究结果表明，将抗凋亡分子整合到CART细胞中可能增强其对抗实体瘤的治疗效果。
表达嵌合抗原受体（CAR）的工程化T细胞对血液系统恶性肿瘤显示出显著的治疗效果。然而，CART细胞对实体瘤的效果较差，主要由于其持久性较弱，这可能是由活化诱导的细胞死亡（AICD）引起的。为克服这一局限，靶向抗原表皮生长因子受体变异体III（EGFRvIII）的CART细胞被修饰以携带抗凋亡分子B细胞淋巴瘤2（Bcl-2），最终构建体被命名为EGFRvIII·CART-Bcl2细胞。与EGFRvIII·CART细胞相比，EGFRvIII·CART-Bcl2细胞在体外表现出更高的增殖、抗凋亡和肿瘤细胞杀伤能力。此外，在宫颈癌异种移植模型中，EGFRvIII·CART-Bcl2细胞比EGFRvIII·CART细胞具有更长的持久率并发挥更好的抗肿瘤效果。综上所述，我们的研究结果表明，将抗凋亡分子整合到CART细胞中可能增强其针对实体瘤的治疗效果。
Engineered T cells expressing chimeric antigen receptors (CARs) have shown remarkable therapeutic effects on haematological malignancies. However, CART cells are less effective on solid tumours mainly due to their weak persistence, which might be caused by activation-induced cell death (AICD). To overcome this limitation, CART cell with the antigen, Epidermal growth factor receptor variant III (EGFRvIII), targeting was modified to carry the anti-apoptotic molecule B cell lymphoma 2 (Bcl-2), and the final construct was named as EGFRvIII·CART-Bcl2 cells. Compared with the EGFRvIII·CART cells, EGFRvIII·CART-Bcl2 cells revealed higher capacities of proliferation, anti-apoptosis and tumour cell killing in vitro. Moreover, EGFRvIII·CART-Bcl2 cells had a longer persistence rate and exerted better anti-tumour effects than EGFRvIII·CART cells in cervical carcinoma xenograft model. Taken together, our findings suggest that incorporating anti-apoptotic molecules into CART cells may enhance its therapeutic effects against solid tumours.
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