Cancer Immunology, Immunotherapy

, Volume 64, Issue 12, pp 1517–1529 | Cite as

Modification of cytokine-induced killer cells with chimeric antigen receptors (CARs) enhances antitumor immunity to epidermal growth factor receptor (EGFR)-positive malignancies

Original Article


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.


Adoptive cellular immunotherapy Cytokine-induced killer cells Chimeric antigen receptor Epidermal growth factor receptor 



Adoptive cellular immunotherapy


Activation-induced cell death


Bispecific antibodies


Chimeric antigen receptor


Cytokine-induced killer


Colorectal cancer


Epidermal growth factor receptor


Enzyme-linked immunosorbent assay


Graft-versus-host disease


Head and neck squamous-cell carcinoma






Lactate dehydrogenase


Monoclonal antibodies


Major histocompatibility complex


Natural killer-like T


Non-small cell lung cancer


Short hairpin RNA




Tumor-associated antigen


Tyrosine kinase inhibitors





We thank Dr. Zhenhua Xu and Prof. Zhaojun Ren for critical review of the manuscript. This work was supported by National Natural Science Foundation of China (No. 81301963), Outstanding Youth Science Foundation of Henan University, Key Project of Scientific and Technological Research of Henan Educational Committee (No. 13B320917), and Science and Technology Development Program of Henan Province (No. 132300410274).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Translational Medicine CenterHuaihe Hospital of Henan UniversityKaifengChina
  2. 2.General SurgeryHuaihe Hospital of Henan UniversityKaifengChina
  3. 3.Department of OncologyHuaihe Hospital of Henan UniversityKaifengChina
  4. 4.Experimental Center of Molecular MedicineLuohe Medical CollegeLuoheChina
  5. 5.Tumor Institute of Yunnan ProvinceThe Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province)KunmingChina

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