Study of immune responses in combined treatment with Gemcitabine and Gvax vaccine in murine model

碩士 === 長庚大學 === 生物醫學研究所 === 106 === Gemcitabine (Gem), a kind of deoxycytidine analog nucleoside, is used as the second-line chemotherapy in many cancer. During DNA synthesis, Gemcitabine is incorporated into the new strand. This leads the cell to inhibit the DNA synthesis and apoptosis. In previous...

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Bibliographic Details
Main Authors: Yu Xin Xie, 謝育昕
Other Authors: J. T. Qiu
Format: Others
Language:en_US
Published: 2018
Online Access:http://ndltd.ncl.edu.tw/handle/r8g7vp
Description
Summary:碩士 === 長庚大學 === 生物醫學研究所 === 106 === Gemcitabine (Gem), a kind of deoxycytidine analog nucleoside, is used as the second-line chemotherapy in many cancer. During DNA synthesis, Gemcitabine is incorporated into the new strand. This leads the cell to inhibit the DNA synthesis and apoptosis. In previous studies, chemotherapy could induce immunogenic cell death and recruit immune system to against death cell antigens. In murine model, Gemcitabine can deplete MDSCs, decrease tumor growth and prolong the survival rate without damage CD4+ and CD8+ T cells. In our previous studies have reported the codon-optimized GM-CSF (Granulocyte-macrophage colony-stimulating factor) gene could enhance the GM-CSF protein expression. Gvax, containing optimized GM-CSF, were irradiated and immunized to mice. We found that Gvax could enhance antitumor effects in mice. In our study, we combine gemcitabine and Gvax, to treat the tumor-bearing mouse. We observed the tumor growth and survival on mice, Then we analyze the immune cells, CD4, CD8 and MDSC from the blood. And we also used ELISA to evaluate IFN-γ and IL-4 secretion. Our results shown that the mice treated with combined treatments had the better tumor-controlling and survival compared to Gvax alone. The combined treatments could inhibit MDSC and have slight effects on CD4+ and CD8+ T cell in tumor-bearing mice And combined treatments could enhance immune response via Th1 and Th2 pathway.