title: Cellular immunotherapy for carcinoma using genetically modified EGFR-specific T lymphocytes.
abstract: Epidermal growth factor receptor (EGFR) is overexpressed in a variety of human malignancies, including pancreatic cancer, breast cancer, colon cancer, and non-small cell lung cancer. Overexpression of EGFR is a predictive marker of therapeutic response and several lines of evidence suggest that EGFR is an excellent target for tumor therapy. However, the effective antitumor capacity of EGFR-specific T cells against EGFR-overexpressing tumor cells has not been fully elucidated. In our previous study, we identified an anti-EGFR single-chain variable fragment (scFv) with specific and high affinity after screening by ribosome display. In this study, the anticancer potential of anti-EGFR scFv was investigated on the basis of cell-targeted therapy. A chimeric antigen receptor (CAR) targeting EGFR was constructed and expressed on the cell membrane of T lymphocytes. These CAR-modified T cells demonstrated antitumor efficacy both in vitro and in vivo. In addition, the safety evaluation showed that CAR-modified lymphocytes have no or very minimal acute systemic toxicity. Taken together, our study provided the experimental basis for clinical application of genetically engineered lymphocytes; moreover, we also evaluate a new and interesting cell therapy protocol.
authors: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Xikun
authors: X
authors: Zhou
authors: Jing
authors: J
authors: Li
authors: Zhen
authors: Z
authors: Wang
authors: Zhongwen
authors: Z
authors: Chen
authors: Ji
authors: J
authors: Qiu
authors: Yinbing
authors: Y
authors: Zhang
authors: Wei
authors: W
authors: Wang
authors: Yu
authors: Y
authors: Ma
authors: Nongyu
authors: N
authors: Huang
authors: Kaijun
authors: K
authors: Cui
authors: Jiong
authors: J
authors: Li
authors: Yu-quan
authors: YQ
authors: Wei
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D015202:Protein Engineering; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D014162:Transfection; D047368:Tumor Burden
chemical_list: D011948:Receptors, Antigen, T-Cell; D066246:ErbB Receptors
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