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Enhanced Anti-tumor Reactivity of Cytotoxic T Lymphocytes Expressing PD-1 Decoy

  • Jae Hun Shin (Research Institute National Cancer Center) ;
  • Hyung Bae Park (Research Institute National Cancer Center) ;
  • Kyungho Choi (Department of Biochemistry and Molecular Biology and Department of Biomedical Sciences, Seoul National University College of Medicine)
  • Received : 2015.12.06
  • Accepted : 2016.03.16
  • Published : 2016.04.30
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Abstract

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.

Keywords

Acknowledgement

We thank Drs. Yosef Refaeli and Garry Nolan for providing us valuable materials. This work was supported by grant from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2013R1A2A2A01009444), Republic of Korea.

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