Research Paper Volume 11, Issue 23 pp 11054—11072

EGFR-specific CAR-T cells trigger cell lysis in EGFR-positive TNBC

Yan Liu 1, 2, , Yehui Zhou 3, , Kuo-Hsiang Huang 1, , Ying Li 1, , Xujie Fang 1, , Li An 1, , Feifei Wang 1, , Qingfei Chen 1, , Yunchao Zhang 1, , Aihua Shi 1, , Shuang Yu 1, 4, , Jingzhong Zhang 1, 4, 5, 6, ,

  • 1 The Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, P. R. China
  • 2 Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, P. R. China
  • 3 The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, P. R. China
  • 4 Xuzhou Medical University, Xuzhou 221004, P. R. China
  • 5 Tianjin Guokeyigong Science and Technology Development Company Limited, Tianjin 300399, P. R. China
  • 6 Zhengzhou Institute of Engineering and Technology Affiliated with SIBET, Zhengzhou 450001, P. R. China

received: August 19, 2019 ; accepted: November 18, 2019 ; published: December 4, 2019 ;

https://doi.org/10.18632/aging.102510
How to Cite

Copyright © 2019 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Triple-negative breast cancer (TNBC) is an aggressive cancer subtype for which effective therapies are lacking. Epidermal growth factor receptor (EGFR) is overexpressed in various types of TNBC cells, and several EGFR-specific immunotherapies have been used to treat cancer patients. Chimeric antigen receptor engineered T (CAR-T) cells have also been used as cancer therapies. In this study, we generated two types of EGFR-specific CAR-modified T cells using lentiviral vectors with DNA sequences encoding the scFv regions of two anti-EGFR antibodies. The cytotoxic and antitumor effects of these CAR-modified T cells were examined in cytokine release and cytotoxicity assays in vitro and in tumor growth assays in TNBC cell line- and patient-derived xenograft mouse models. Both types of EGFR-specific CAR-T cells were activated by high-EGFR-expressing TNBC cells and specifically triggered TNBC cell lysis in vitro. Additionally, the CAR-T cells inhibited growth of cell-line- and patient-derived xenograft TNBC tumors in mice. These results suggest that EGFR-specific CAR-T cells might be a promising therapeutic strategy in patients with high-EGFR-expressing TNBC.

Abbreviations

TNBC: Triple-negative breast cancer; EGFR: Epidermal growth factor receptor; CAR-T: chimeric antigen receptor engineered T cells; PDX: Patient-derived xenograft; CLDX: Cell-line-derived xenograft; ER: estrogen receptor; PR: progesterone receptor; HER2: human epidermal growth factor receptor 2; scFv: Single-chain variable fragment; IL2: Interleukin 2; IL4: Interleukin 4; PBMCs: Peripheral blood mononuclear cells; siRNA: Small interfering RNA.