State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Neoplasia. 2013 May;15(5):544-53. doi: 10.1593/neo.13168.
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.
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靶点。然而，EGFR 特异性 T 细胞对 EGFR 过表达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后鉴定出了一种具有特异性和高亲和力的抗 EGFR 单链可变片段（scFv）。在这项研究中，基于细胞靶向治疗研究了抗 EGFR scFv 的抗癌潜力。构建了一种针对 EGFR 的嵌合抗原受体（CAR），并在 T 淋巴细胞的细胞膜上表达。这些 CAR 修饰的 T 细胞在体外和体内均显示出抗肿瘤功效。此外，安全性评估表明，CAR 修饰的淋巴细胞没有或只有非常轻微的急性全身毒性。总之，我们的研究为基因工程淋巴细胞的临床应用提供了实验基础；此外，我们还评估了一种新的、有趣的细胞治疗方案。
