Study the immune responses of both T lymphocytes and dendritic cells to a high-dose GM-CSF-secreting cell-based vaccine in murine TC-1 cancer model

• Main Authors: Guo Shiang Jang, 張國祥
• Other Authors: J. T. Qiu
• Format: Others
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/18839765932401606662

碩士 === 長庚大學 === 生物醫學研究所 === 99 === Cervical cancer is the second largest cause of cancer-related death in women Worldwide, which occurs following persistent infection with specific high-risk human papillomaviruses (HPV). Even though the prophylactic vaccines were approved and became available in the market in recent years. There also need therapeutic vaccines to combat high-risk HPV-associated cancers of those had been infected. In order to increase tumor antigen presentation of therapeutic vaccines, we previously modified wild-type GM-CSF gene (wtGM) into codon-optimized GM-CSF (cGM), and then used lentivirus as a vector to deliver GM-CSF gene into a HPV-16 E6/E7 transformed cell line, TC-1. It was verified that TC-1/cGM cells significantly increased steady-state mRNA levels of GM-CSF and further enhanced GM-CSF protein expression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor and has profound effects on the functional activities of various leukocytes including T-cells and dendritic cells. In this study, the mice were inoculated with irradiated TC-1/cGM cell-based vaccine, and evaluated its effects on antigen-specific T-cell and dendritic cells (DCs) proliferation and activation by flow cytometric analysis. The antitumor immunity in vivo was monitored using a non-invasive animal position-emission tomography (microPET) imaging. It showed that mice vaccinated with TC-1 or TC-1/wtGM increased a lower level of CD8+ T-cells and DCs immune response. However, administration of TC-1/cGM vaccine revealed more potent immunity to elicit anti-tumor efficacy.