肿瘤细胞治疗研究
英文原题：Ligand-Based CAR-T Cells Targeting EGFR Exhibit Favorable Antitumor Effects Against Gynecologic Malignancies.
Ligand-Based CAR-T Cells Targeting EGFR Exhibit Favorable Antitumor Effects Against Gynecologic Malignancies.
基于配体的 EGFR CAR-T 细胞可能成为多种妇科恶性肿瘤的有前景疗法。
已有报道显示，表皮生长因子受体（EGFR）在妇科恶性肿瘤中表达升高。然而，现有分子靶向EGFR治疗妇科恶性肿瘤的临床疗效尚未得到证实。本研究考察基于配体的EGFR嵌合抗原受体（CAR）T细胞对妇科恶性肿瘤的抗肿瘤作用。首先采用免疫组织化学检测患者样本中的EGFR表达。患者样本中，卵巢癌、子宫内膜癌和宫颈癌的EGFR阳性率分别为41%、82%和79%。其次，通过piggyBac介导的基因转移制备基于配体的EGFR CAR-T细胞。成功生成CAR阳性率高且初始/干细胞记忆样T细胞比例较高的EGFR CAR-T细胞。最后，我们研究EGFR CAR-T细胞对妇科恶性肿瘤的抗肿瘤效应。将EGFR CAR-T细胞与6种EGFR阳性妇科癌细胞系共培养；与模拟转导T细胞相比，EGFR CAR-T细胞显著抑制所有6种细胞系的生长。体内研究中，将妇科癌细胞系植入腹腔建立荷瘤小鼠模型，并腹腔给予EGFR CAR-T、CD19 CAR-T或PBS。与CD19 CAR-T或PBS组相比，EGFR CAR-T组小鼠肿瘤负荷显著降低，生存期也显著延长。总之，基于配体的EGFR CAR-T细胞可能是治疗多种妇科恶性肿瘤的有前景疗法。
Epidermal growth factor receptor (EGFR) has been reported to be overexpressed in gynecologic malignancies. However, the clinical efficacy of existing molecular EGFR-targeted therapies against gynecologic malignancies has not been demonstrated. In this study, we investigated the antitumor effects of ligand-based EGFR chimeric antigen receptor (CAR)-T cells on gynecologic malignancies. First, we evaluated EGFR expression in patient samples using immunohistochemistry. EGFR positivity was observed in 41%, 82%, and 79% of ovarian, endometrial, and cervical cancer in patient samples, respectively. Second, we generated ligand-based EGFR CAR-T cells via piggyBac-mediated gene transfer. EGFR CAR-T cells were successfully generated with high CAR positivity and a high proportion of na ve/stem cell memory-like T cells. Finally, we investigated the antitumor effects of EGFR CAR-T cells on gynecologic malignancies. EGFR CAR-T cells were co-cultured with six EGFR-positive gynecologic cancer cell lines. The growth of all six gynecologic cancer cell lines was significantly suppressed by EGFR CAR-T cells compared to mock T cells. In in vivo studies, tumor-bearing mice implanted with gynecologic cancer cell lines in their intraperitoneal cavity were administered EGFR CAR-T cells, CD19 CAR-T cells, or PBS intraperitoneally. Mice treated with EGFR CAR-T cells displayed a significantly decreased tumor burden compared to those treated with either CD19 CAR-T cells or PBS. Additionally, mice treated with EGFR CAR-T cells had a significantly longer survival than the other groups. In summary, ligand-based EGFR CAR-T cells may be a promising therapy for various gynecologic malignancies.
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