Reconstructed Adeno-Associated Virus with the Extracellular Domain of Murine PD-1 Induces Antitumor Immunity

• DOI: 10.7314/apjcp.2012.13.8.4031
• Publication Date: 2013-02-06T07:02:58Z
• Authors: Osama A.O. Elhag; Xiao-Jing Hu; Zhang Wen-Ying; Xiong Li; Yong-Ze Yuan; Ling-Feng Deng; De-Li Liu; Ying-Le Liu; Geng Hui
• Keywords: Splenocyte

Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade this pathway has been proven enhance cytotoxic activity mediate antitumor therapy. Here we evaluated anti-tumor efficacy AAV-mediated delivery extracellular domain murine PD-1 (sPD-1) site. Material Methods: An rAAV vector was constructed in which expression sPD-1, known regulator TCR signals, driven human cytomegalovirus immediate early promoter (CMV-P), using triple plasmid transfection system. Tumor-bearing mice were then treated with AAV/sPD1 construct sPD-1 tissues determined semi quantitative RT-PCR, weights splenocytes measured. Results: Analysis homogenates revealed mRNA be significantly overexpressed rAAV/sPD-1 as compared control levels. Its use for local gene therapy at inoculation site H22 hepatoma cells could inhibit growth, also enhancing lysis lymphocytes stimulated specifically an antigen. In addition, found expressed on surfaces activated CD8+ T cells. Conclusion: This study confirmed that soluble molecule reduce microenvironment inhibitory effects cytotoxicity. suggests it might potential target development therapies augment T-cell responses patients malignancies.