Enhanced anti-tumor reactivity of cytotoxic T lymphocytes expressing PD-1 decoy

Jae Hun Shin, Hyung Bae Park, Kyungho Choi

Research output: Contribution to journalArticle

3 Scopus citations

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-γsecretion 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.

Original languageEnglish
Pages (from-to)134-139
Number of pages6
JournalImmune Network
Volume16
Issue number2
DOIs
StatePublished - 1 Jan 2016

Keywords

  • PD-1
  • PD-1 decoy
  • PD-L1
  • T lymphocytes

Cite this