title: Modification of cytokine-induced killer cells with chimeric antigen receptors (CARs) enhances antitumor immunity to epidermal growth factor receptor (EGFR)-positive malignancies.
abstract: Epidermal growth factor receptor (EGFR, ErbB1, Her-1) is a cell surface molecule overexpressing in a variety of human malignancies and, thus, is an excellent target for immunotherapy. Immunotherapy targeting EGFR-overexpressing malignancies using genetically modified immune effector cells is a novel and promising approach. In the present study, we have developed an adoptive cellular immunotherapy strategy based on the chimeric antigen receptor (CAR)-modified cytokine-induced killer (CAR-CIK) cells specific for the tumor cells expressing EGFR. To generate CAR-CIK cells, a lentiviral vector coding the EGFR-specific CAR was constructed and transduced into the CIK cells. The CAR-CIK cells showed significantly enhanced cytotoxicity and increased production of cytokines IFN-γ and IL-2 when co-cultured with EGFR-positive cancer cells. In tumor xenografts, adoptive immunotherapy of CAR-CIK cells could inhibit tumor growth and prolong the survival of EGFR-overexpressing human tumor xenografts. Moreover, tumor growth inhibition and prolonged survival in mice with EGFR(+) human cancer were associated with the increased persistence of CAR-CIK cells in vivo. Our study indicates that modification with EGFR-specific CAR strongly enhances the antitumor activity of the CIK cells against EGFR-positive malignancies.
authors.affiliation: Translational Medicine Center, Huaihe Hospital of Henan University, No. 115, Simon Street, Kaifeng, 475001, Henan Province, China.
authors.forename: Xuequn
authors.initials: X
authors.lastname: Ren
authors.affiliation: General Surgery, Huaihe Hospital of Henan University, Kaifeng, 475001, Henan Province, China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, 475001, Henan Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Experimental Center of Molecular Medicine, Luohe Medical College, Luohe, 462002, Henan Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Translational Medicine Center, Huaihe Hospital of Henan University, No. 115, Simon Street, Kaifeng, 475001, Henan Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: An
authors.affiliation: Tumor Institute of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 650118, Yunnan, China.
authors.forename: Xicai
authors.initials: X
authors.lastname: Wang
authors.affiliation: Translational Medicine Center, Huaihe Hospital of Henan University, No. 115, Simon Street, Kaifeng, 475001, Henan Province, China. mike0092@126.com.
authors.forename: Guanchang
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Translational Medicine Center, Huaihe Hospital of Henan University, No. 115, Simon Street, Kaifeng, 475001, Henan Province, China. dawning.zuo@gmail.com.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Zuo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D055612:Cytokine-Induced Killer Cells / Q000166:cytology / Q000276:immunology*; D066246:ErbB Receptors / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D011946:Receptors, Antigen / Q000235:genetics / Q000276:immunology*; D017471:Receptors, Interferon / Q000276:immunology / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D066246:ErbB Receptors; D007376:Interleukin-2; D011946:Receptors, Antigen; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C512478:EGFR protein, human
keywords: Adoptive cellular immunotherapy; Chimeric antigen receptor; Cytokine-induced killer cells; Epidermal growth factor receptor