CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Anti-HER2 scFv-CCL19-IL7 recombinant protein inhibited gastric tumor growth in vivo.
Anti-HER2 scFv-CCL19-IL7 recombinant protein inhibited gastric tumor growth in vivo.
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HER2靶向治疗(如单克隆抗体和CAR-T 细胞疗法)已用于多种癌症。然而,抗HER2 CAR-T 细胞疗法受到生产流程昂贵及细胞因子风暴、“靶向肿瘤但伤及正常组织”等致命副作用的限制。抗HER2单克隆抗体治疗实体瘤也因患者出现不同机制的耐药而受阻。因此,重组蛋白技术具有吸引力,可能毒性更低且成本更低。本研究制备了一种靶向HER2的重组蛋白,将抗HER2单链可变片段(scFv)与CCL19和IL-7融合(HCI融合蛋白)。结果显示,该重组蛋白可诱导免疫细胞特异性裂解HER2阳性胃癌细胞,并通过趋化自身免疫细胞浸润肿瘤组织和活化T细胞,在异种移植模型中抑制胃癌生长。综上,HCI融合蛋白有望作为后续临床药物用于治疗HER2阳性胃癌。
HER-2 targeted therapies, such as monoclonal antibodies (mAbs) and CAR-T cell therapy have been applied in the treatment of various of cancers.
However, the anti-HER2 CAR-T cell therapy are limited by its expensive production procedure and fatal side effects such as cytokine storm or "On target, off tumor". The application of anti-HER2 mAbs to the soild tumor are also plagued by the patients resistant with different mechanisms.
Thus, the recombinant protein technology can be presented as an attractive methods in advantage its less toxic and lower cost. In this study, we produced a HER-2-targeting recombinant protein, which is the fusion of the anti-HER-2 single chain fragment variable domain, CCL19 and IL7 (HCI fusion protein).
Our results showed that the recombinant protein can induce the specific lysis effects of immune cells on HER-2-positive gastric tumor cells and can suppress gastric tumor growth in a xenograft model by chemotactic autoimmune cell infiltration into tumor tissues and activated T cells. Taken together, our results revealed that the HCI fusion protein can be applied as a subsequent clinical drug in treating HER-2 positive gastric tumors.
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