Study the Immune Response of T Lymphocyte to a High-Dose GMCSF-Secreting Tumor Cell-Based Vaccine in Mice

The oncogenic pathways of cervical cancer is caused by persistent infection in the human body via several high-risk type of human papilloma virus (human papillomaviruses, HPV). In recent years, despite the preventive vaccine against HPV has been approved to come out and get a good effectiveness but in clinical still need therapeutic vaccine against persistent infection in women who have been infected with high risk HPV types. In order to enhance the antigen presenting ability of HPV vaccine produced, we modify codon usage of granulocyte-macrophages stimulating factor (GM-CSF) of mice but without changing amino acid sequence. As a consequent of modifying codon, it improved the stability of the mRNA, thereby enhancing the expression amount of the protein. By using lentivirus vectors, we transfected mcGM-CSF into HPV oncogenic E6/E7 of mouse tumor cells, TC-1. Since GM-CSF is an important hematopoietic growth factor, activating the immune system, including T cells and dendritic cells, will be used as a vaccine adjuvant. In this project, we will vaccinate radiated TC-1, TC-1/wtGM (wild-type GM-CSF) or TC -1/cGM (codon-optmized GMCSF) in mice, and analysis antigen-specific CD8 + T cells and dendritic cells response by flow cytometry. In addition, some papers indicated that several vaccinations will induce suppressor T cells and MDSC cells. In this project, we will also analyze whether the same phenomenon will be occurred at and to investigate the mechanism of this induction. We had studied the DC and CD4 cells activity in IL-15Ra-/- mice and published two papers on this area. We will apply the IL-15Ra-/- mice in cell base vaccine model to dissect the immune regulations in cancer tolerance. We will establish the TC-1 tumor-bearing mice (both wild type and IL-15Ra-/- mice) and analyze the frequency and suppressive activities of naturally occurring Treg cells which are reduced or impaired in IL-15R-/- mice compared to WT counterparts. Through this project, we will understand the immune response produced by therapeutic vaccines in animal models, and these results will be applied in the clinic treatment.

Project ID:PC10301-0551
External Project ID:NSC102-2314-B182-041-MY2