Cellular Immunotherapy for Carcinoma Using Genetically Modified EGFR-Specific T Lymphocytes
Cellular Immunotherapy for Carcinoma Using Genetically Modified EGFR-Specific T Lymphocytes
复制标题
使用基因修饰的 EGFR 特异性 T 淋巴细胞进行癌症细胞免疫疗法。
DOI：
10.1593/neo.13168
复制
发表时间：
2013-05-01
期刊：
影响因子：
4.8
通讯作者：
Wei, Yu-quan
中科院分区：
文献类型：
--
作者：
Zhou, Xikun;Li, Jing;Wei, Yu-quan
表皮生长因子受体（EGFR）在多种人类恶性肿瘤中过表达，包括胰腺癌、乳腺癌、结肠癌和非小细胞肺癌。EGFR的过表达是治疗反应的预测标志物，有几条证据表明EGFR是肿瘤治疗的一个极好的靶点。然而，egfr特异性T细胞对过表达egfr的肿瘤细胞的有效抗肿瘤能力尚未完全阐明。在我们之前的研究中，我们通过核糖体展示筛选，鉴定出具有特异性和高亲和力的抗egfr单链可变片段（scFv）。本研究在细胞靶向治疗的基础上，探讨了抗egfr scFv的抗癌潜力。构建了一种靶向EGFR的嵌合抗原受体（CAR），并在T淋巴细胞细胞膜上表达。这些car修饰的T细胞在体内和体外都显示出抗肿瘤的功效。此外，安全性评估显示car修饰淋巴细胞没有或非常小的急性全身毒性。本研究为基因工程淋巴细胞的临床应用提供了实验依据；此外，我们还评估了一种新的有趣的细胞治疗方案。
Epidermal growth factor receptor (EGFR) is overexpressed in a variety of human malignancies, including pancreatic cancer, breast cancer, colon cancer, and non-small cell lung cancer. Overexpression of EGFR is a predictive marker of therapeutic response and several lines of evidence suggest that EGFR is an excellent target for tumor therapy. However, the effective antitumor capacity of EGFR-specific T cells against EGFR-overexpressing tumor cells has not been fully elucidated. In our previous study, we identified an anti-EGFR single-chain variable fragment (scFv) with specific and high affinity after screening by ribosome display. In this study, the anticancer potential of anti-EGFR scFv was investigated on the basis of cell-targeted therapy. A chimeric antigen receptor (CAR) targeting EGFR was constructed and expressed on the cell membrane of T lymphocytes. These CAR-modified T cells demonstrated antitumor efficacy both in vitro and in vivo. In addition, the safety evaluation showed that CAR-modified lymphocytes have no or very minimal acute systemic toxicity. Taken together, our study provided the experimental basis for clinical application of genetically engineered lymphocytes; moreover, we also evaluate a new and interesting cell therapy protocol.