title: Chimeric antigen receptor-modified T Cells inhibit the growth and metastases of established tissue factor-positive tumors in NOG mice.
abstract: Chimeric antigen receptor (CAR)-modified T cell (CAR T) is a promising therapeutic option for patients with cancer. Such an approach requires the identification of tumor-specific antigen targets that are expressed in solid tumors. We developed a new third-generation CAR directed against tissue factor (TF), a surface molecule overexpressed in some types of lung cancer, melanoma and other cancers. First, we demonstrated by immunohistochemistry that TF was overexpressed in squamous cell carcinoma and adenocarcinoma of non-small cell lung cancer (NSCLC) and melanoma using a human tissue microarray. In the presence of TF-positive cancer cells, the CAR-modified T cells (TF-CAR T) were highly activated and showed specific cytotoxicity to TF-positive cancer cells in vitro. In established s.c. xenograft and lung metastasis models, TF-CAR T cells could significantly suppress the growth of s.c. xenograft and metastasis of TF-positive cancer cells. Additionally, the safety evaluation of TF-CAR T cells in vivo showed that the treatment did not cause obvious toxicity in mice. Taken together, these findings indicate that TF-CAR T cells might be a novel potential therapeutic agent for the treatment of patients with TF-positive cancers.
authors.affiliation: Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Huizhong
authors.initials: H
authors.lastname: Li
authors.affiliation: Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Tian
authors.affiliation: Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China.
authors.forename: Junnian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000556:secondary / Q000628:therapy*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000378:metabolism / Q000556:secondary / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism / Q000556:secondary / Q000628:therapy*; D002465:Cell Movement; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D061986:MCF-7 Cells; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D013925:Thromboplastin / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D013925:Thromboplastin
keywords: T cell; chimeric antigen receptor; lung cancer; melanoma; tissue factor