PMID- 26684028 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20201226 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 3 DP - 2016 Jan 19 TI - Adoptive immunotherapy using T lymphocytes redirected to glypican-3 for the treatment of lung squamous cell carcinoma. PG - 2496-507 LID - 10.18632/oncotarget.6595 [doi] AB - 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. FAU - Li, Kesang AU - Li K AD - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Pan, Xiaorong AU - Pan X AD - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Bi, Yanyu AU - Bi Y AD - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Xu, Wen AU - Xu W AD - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Chen, Cheng AU - Chen C AD - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Gao, Huiping AU - Gao H AD - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Shi, Bizhi AU - Shi B AD - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Jiang, Hua AU - Jiang H AD - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Yang, Shengli AU - Yang S AD - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Jiang, Liyan AU - Jiang L AD - Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Li, Zonghai AU - Li Z AD - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (GPC3 protein, human) RN - 0 (Glypicans) RN - 0 (Receptors, Antigen, T-Cell) SB - IM MH - Animals MH - Apoptosis MH - Blotting, Western MH - Carcinoma, Squamous Cell/immunology/metabolism/pathology/*therapy MH - Cell Proliferation MH - Flow Cytometry MH - Glypicans/*immunology/metabolism MH - Humans MH - Immunoenzyme Techniques MH - *Immunotherapy, Adoptive MH - Lung Neoplasms/immunology/metabolism/pathology/*therapy MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - Receptors, Antigen, T-Cell/metabolism MH - T-Lymphocytes, Cytotoxic/*immunology MH - Tumor Cells, Cultured MH - Xenograft Model Antitumor Assays PMC - PMC4823050 OTO - NOTNLM OT - CAR T cell OT - chimeric antigen receptor OT - glypican-3 OT - lung squamous cell carcinoma COIS- CONFLICTS OF INTEREST Dr. Zonghai Li has ownership interests (including patents) of anti-GPC3 CAR-T. No potential conflicts of interest were disclosed by the other authors. EDAT- 2015/12/20 06:00 MHDA- 2016/12/15 06:00 PMCR- 2016/01/19 CRDT- 2015/12/20 06:00 PHST- 2015/08/12 00:00 [received] PHST- 2015/11/21 00:00 [accepted] PHST- 2015/12/20 06:00 [entrez] PHST- 2015/12/20 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2016/01/19 00:00 [pmc-release] AID - 6595 [pii] AID - 10.18632/oncotarget.6595 [doi] PST - ppublish SO - Oncotarget. 2016 Jan 19;7(3):2496-507. doi: 10.18632/oncotarget.6595.