title: Enhanced Anti-tumor Reactivity of Cytotoxic T Lymphocytes Expressing PD-1 Decoy.
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.
authors.affiliation: Research Institute National Cancer Center, Goyang, Gyeonggi-do 10408, Korea.
authors.forename: Jae Hun
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Research Institute National Cancer Center, Goyang, Gyeonggi-do 10408, Korea.; Department of Biochemistry and Molecular Biology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Hyung Bae
authors.initials: HB
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Kyungho
authors.initials: K
authors.lastname: Choi
keywords: PD-1; PD-1 decoy; PD-L1; T lymphocytes