Enhanced Anti-tumor Reactivity of Cytotoxic T Lymphocytes Expressing PD-1 Decoy.
- Author:
Jae Hun SHIN
1
;
Hyung Bae PARK
;
Kyungho CHOI
Author Information
- Publication Type:Brief Communication
- Keywords: PD-1; PD-L1; T lymphocytes; PD-1 decoy
- MeSH: Adoptive Transfer; Animals; Antibodies, Blocking; Autoimmunity; Cell- and Tissue-Based Therapy; Humans; Lymphocytes; Mice; T-Lymphocytes; T-Lymphocytes, Cytotoxic*; Zidovudine
- From:Immune Network 2016;16(2):134-139
- CountryRepublic of Korea
- Language:English
- 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.
