Adoptive immunotherapy using T lymphocytes redirected to glypican-3 for the treatment of lung squamous cell carcinoma

作者：Li, Kesang; Pan, Xiaorong; Bi, Yanyu; Xu, Wen; Chen, Cheng; Gao, Huiping; Shi, Bizhi; Jiang, Hua; Yang, Shengli; Jiang, Liyan; Li, Zonghai^*

来源：Oncotarget, 2016, 7(3): 2496-2507.

DOI：10.18632/oncotarget.6595

• lung squamous cell carcinoma
• chimeric antigen receptor
• glypican-3
• CAR T cell

There are unmet medical needs for patients with lung squamous cell carcinoma (LSCC). Therefore, in this study, we explored the antitumor potential of third-generation glypican 3 (GPC3)-redirected chimeric antigen receptor (CAR)-engineered T lymphocytes (CARgpc3 T cells) in tumor models of LSCC. First, we demonstrated by immunohistochemistry (IHC) that GPC3 was expressed in 66.3% of LSCC samples and in 3.3% of lung adenocarcinoma (LAD) samples but not in normal lung tissues. In the presence of GPC3-positive LSCC cells, CARgpc3 T cells were highly activated and increased in number. CARgpc3 T cells could specifically lyse GPC3-positive LSCC cells in vitro. In two established LSCC xenograft models, CARgpc3 T cells could almost completely eliminate the growth of GPC3-positive cells. Additionally, the CARgpc3 T cells were able to persist in vivo and efficiently infiltrate the cancerous tissues. Taken together, these findings indicate that CARgpc3 T cells might be a novel potential therapeutic agent for the treatment of patients with LSCC.

• 出版日期2016-1-19
• 单位上海交通大学; 上海市肿瘤研究所