肿瘤细胞治疗研究
英文原题：Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma.
我们的结果提示，CAR T 细胞可在体外和体内特异性清除 Tn-MUC1 阳性 ICC 细胞，而不清除 Tn-MUC1 阴性 ICC 细胞。
肝内胆管癌（ICC）是常见肝脏恶性肿瘤，患者5年生存率有限，因此亟需探索新的治疗方法。CAR-T（CAR-T）细胞疗法是极具前景的癌症治疗方式。尽管已有多个研究团队在实体瘤模型中考察靶向MUC1的CAR-T细胞，但此前尚无靶向Tn-MUC1的CAR-T细胞用于ICC的报道。本研究证实Tn-MUC1是ICC的潜在治疗靶点，且其表达水平与ICC患者不良预后呈正相关。更重要的是，我们成功开发出有效靶向Tn-MUC1阳性ICC肿瘤的CAR-T细胞，并考察其抗肿瘤活性。结果提示，该CAR-T细胞可在体内外特异性清除Tn-MUC1阳性ICC细胞，但不能清除Tn-MUC1阴性ICC细胞。因此，本研究有望为ICC治疗提供新的策略和思路。
Intrahepatic cholangiocarcinoma (ICC) is a common malignancy arising from the liver with limited 5-year survival. Thus, there is an urgency to explore new treatment methods. Chimeric antigen receptor T (CAR T) cell therapy is a very promising cancer treatment. Though, several groups have investigated CAR T cells targeting MUC1 in solid cancer models, Tn-MUC1-targeted CAR T cells have not yet to be reported in ICC. In this study, we confirmed Tn-MUC1 as a potential therapeutic target for ICC and demonstrated that its expression level was positively correlated with the poor prognosis of ICC patients. More importantly, we successfully developed effective CAR T cells to target Tn-MUC1-positive ICC tumors and explored their antitumor activities. Our results suggest the CAR T cells could specifically eliminate Tn-MUC1-positive ICC cells, but not Tn-MUC1-negative ICC cells, in vitro and in vivo. Therefore, our study is expected to provide new therapeutic strategies and ideas for the treatment of ICC.
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