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

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.

Keywords

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

Abbreviations

ACI

Adoptive cellular immunotherapy

AICD

Activation-induced cell death

BsAbs

Bispecific antibodies

CAR

Chimeric antigen receptor

CIK

Cytokine-induced killer

CRC

Colorectal cancer

EGFR

Epidermal growth factor receptor

ELISA

Enzyme-linked immunosorbent assay

GVHD

Graft-versus-host disease

HNSCC

Head and neck squamous-cell carcinoma

IFN-γ

Interferon-γ

IL-2

Interleukin-2

LDH

Lactate dehydrogenase

mAbs

Monoclonal antibodies

MHC

Major histocompatibility complex

NKT

Natural killer-like T

NSCLC

Non-small cell lung cancer

shRNA

Short hairpin RNA

SPF

Specific-pathogen-free

TAA

Tumor-associated antigen

TKIs

Tyrosine kinase inhibitors

TM

Transmembrane

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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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