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Tumor Biology

, Volume 37, Issue 1, pp 799–806 | Cite as

Engineered cytotoxic T lymphocytes with AFP-specific TCR gene for adoptive immunotherapy in hepatocellular carcinoma

  • Longhao Sun
  • Hao Guo
  • Ruoyu Jiang
  • Li Lu
  • Tong Liu
  • Xianghui He
Original Article

Abstract

Alpha-fetoprotein (AFP) is overexpressed in hepatocellular carcinoma (HCC) and could serve as a tumor-associated antigen (TAA) and potential target for adoptive immunotherapy. However, low frequency and severe functional impairment of AFP-specific T cells in vivo hamper adoptive infusion. TAA-specific T cell receptor (TCR) gene transfer could be an efficient and reliable alternation to generate AFP-specific cytotoxic T lymphocytes (CTLs). Autologous dendritic cells (DC) pulsed with AFP158-166 peptides were used to stimulate AFP-specific CTLs. TCR α/β chain genes of AFP-specific CTLs were cloned and linked by 2A peptide to form full-length TCR coding sequence synthesized into a lentiviral vector. Nonspecific activated T cells were engineered by lentivirus infection. Transgenetic CTLs were evaluated for transfection efficiency, expression of AFP158-166-specific TCR, interferon (IFN)-γ secretion, and specific cytotoxicity toward AFP+ HCC cells in vitro and in vivo. Flow cytometry revealed the AFP158-166-MHC-Pentamer positive transgenetic CTLs was 9.86 %. The number of IFN-γ secretion T cells and the specific cytotoxicity toward HpeG2 in vitro and in tumor-bearing NOD/SCID mice were significantly raised in transgenetic CTLs than that of AFP158-166-specific CTLs obtained by peptide-pulsed DCs or control group. TCR gene transfer is a promising strategy to generate AFP158-166-specific CTLs for the treatment of HCC.

Keywords

AFP158-166-specific T cell receptor Transgenetic Adoptive immunotherapy Hepatocellular carcinoma 

Notes

Acknowledgments

This work was supported by National Natural Science Foundation of China Grants No.81172167.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Longhao Sun
    • 1
  • Hao Guo
    • 1
  • Ruoyu Jiang
    • 1
  • Li Lu
    • 1
  • Tong Liu
    • 1
  • Xianghui He
    • 1
  1. 1.Department of General SurgeryTianjin Medical University General HospitalTianjinChina

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