Journal
ONCOTARGET
Volume 7, Issue 3, Pages 2496-2507Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6595
Keywords
lung squamous cell carcinoma; chimeric antigen receptor; glypican-3; CAR T cell
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Funding
- State Key Laboratory of Oncogenes and Related Genes [91-14-12]
- Shanghai Science and Technology Development Funds [12JC1408300]
- Shanghai Rising-Star Program [13QA1403300]
- One Hundred Talents Scientific Research Projects of Health System in Shanghai [XBR2013123]
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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.
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