Monoclonal antibody 3H11 chimeric antigen receptors enhance T cell effector function and exhibit efficacy against gastric cancer.

Monoclonal antibody 3H11 chimeric antigen receptors enhance T cell effector function and exhibit efficacy against gastric cancer.
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单克隆抗体3H11嵌合抗原受体增强T细胞效应功能并表现出抗胃癌功效

DOI:
10.3892/ol.2018.8255
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发表时间:
2018-05
期刊:
影响因子:
2.9
通讯作者:
Ji J
Ji J
中科院分区:
医学4区
文献类型:
--
作者:
Han H;Wang S;Hu Y;Li Z;Yang W;Lv Y;Wang L;Zhang L;Ji J

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尽管针对某些类型实体瘤的嵌合抗原受体 T 细胞 (CAR-T) 疗法已用于临床试验,但仍然需要能够靶向胃癌 (GC) 的新型 CAR。在我们之前的研究中,用五种人GC细胞系免疫产生的单克隆抗体3H11(mAb 3H11)被证明具有93.5%的阳性反应,膜位置清晰,GC组织中癌细胞染色超过5%。在本研究中,3H11-CAR 被设计用于改良的 T 细胞疗法。首先,已证实mAb 3H11的单链可变片段(scFV)(称为scFV-3H11)表现出与天然抗体相似的活性。此外,scFV-3H11 CAR-T细胞能够在体外杀死肿瘤细胞,同时增加白细胞介素2和干扰素-γ的分泌,并在体内减轻GC细胞系和患者来源的GC细胞的肿瘤负荷。总之,scFV-3H11 CAR 可能具有治疗 mAb 3H11 阳性 GC 的潜力。
Although chimeric antigen receptor T cell (CAR-T) therapies for certain types of solid tumors have been used in clinical trials, novel CARs that are able to target gastric cancer (GC) are still required. In our previous study, monoclonal antibody 3H11 (mAb 3H11), generated from immunization with five human GC cell lines, was demonstrated to have a 93.5% positive reaction with a clear membrane location and more than 5% cancer cell staining in GC tissues in our previous study. In the present study, 3H11-CARs were designed for modified T cell therapy. To begin with, it was confirmed that the single-chain variable fragment (scFV) of the mAb 3H11, known as scFV-3H11, exhibited similar activity with the natural antibody. In addition, scFV-3H11 CAR-T cells are able to kill tumor cells accompanied with increased interleukin-2 and interferon-γ secretion in vitro, and reduced the tumor burden in GC cell lines and patient-derived GC cells in vivo. In conclusion, scFV-3H11 CARs may have the potential to treat mAb 3H11-positive GC.
病毒特异性的T细胞设计为共表达肿瘤特异性受体:神经母细胞瘤个体中的持久性和抗肿瘤活性。
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