肺鳞癌是一种常见的肺癌，严重危害着人类健康，亟需有效的靶向药物。近日，由上海市肿瘤研究所癌基因及相关基因国家重点实验室研究员李宗海团队与上海市胸科医院呼吸内科姜丽岩主任合作的关于磷脂酰肌醇聚糖-3(GPC3)重定向T细胞用于治疗肺鳞癌的临床前研究于Oncotarget上在线发表。结果显示，经改造的CAR-GPC3 T细胞在体外能够特异杀伤GPC3阳性的肺鳞癌细胞，在体内能够有效地清除GPC3阳性的肺鳞癌移植瘤；此外，CAR-GPC3 T细胞能在小鼠体内持久地存活。此研究揭示了CAR-GPC3 T细胞治疗不仅有望治疗肝细胞癌，同时将为肺鳞癌的治疗提供可行方案。
据不完全统计，GPC3在70%的肝细胞癌患者中呈阳性表达；而在肺鳞癌人群中阳性率亦有60%。由科济生物医药（上海）有限公司资助的GPC3-CART细胞最先被用于治疗肝细胞癌的临床研究。目前相关临床试验正在上海交通大学医学院附属仁济医院开展，有意向的病人或病人家属可联系咨询了解。相关信息，可登陆公司网站www.carsgen.com/zh-hans进行查询。
ABSTRACT
There are unmetmedical needs for patients with lung squamous cell carcinoma (LSCC). Therefore,in this study, we explored the antitumor potential of third-generation glypican3 (GPC3)-redirected chimeric antigen receptor (CAR)-engineered T lymphocytes(CARgpc3 T cells) in tumor models of LSCC. First, we demonstrated byimmunohistochemistry (IHC) that GPC3 was expressed in 66.3% of LSCC samples andin 3.3% of lung adenocarcinoma (LAD) samples but not in normal lung tissues. Inthe presence of GPC3-positive LSCC cells, CARgpc3 T cells were highly activatedand increased in number. CARgpc3 T cells could specifically lyse GPC3-positiveLSCC cells in vitro. In two established LSCC xenograft models, CARgpc3 Tcells could almost completely eliminate the growth of GPC3-positive cells.Additionally, the CARgpc3 T cells were able to persist in vivo andefficiently infiltrate the cancerous tissues. Taken together, these findingsindicate that CARgpc3 T cells might be a novel potential therapeutic agent forthe treatment of patients with LSCC.
