Study the immune modulation by regulatory T cell in multiple vaccinations of GM-CSF-secreting cell-based vaccine
| Autor: | Ya Fang Cheng, 鄭雅方 |
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| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 Immunotherapy is playing a critical role in the treatment of cancers. It has been reported that tumor-cell based vaccine can induce tumor-specific T cell responses to prime systemic antitumor immunity, and GM-CSF is now widely used as an adjuvant in immunotherapy protocols. Our previous studies have shown co-immunization of plasmids encoded codon-optimized GM-CSF sequence with DNA vaccine would induce potent antibody and cytotoxic T lymphocyte responses. However, weather vaccination strategies that given multiple times would induce the effective antitumor immunity remain unclear. According to recent studies, multiple vaccinations of GM-CSF secreting tumor resulted in limiting the efficacy of vaccine by the increase level of regulatory T (Treg) cells. In our study, we used codon-optimized GM-CSF-secreting cell-based vaccine, which expressed high level GM-CSF, combined with multiple vaccination strategies to investigate the immune modulation by regulatory T (Treg) cells. Mice were subcutaneously injected with 106 irradiated cells each site, and we sacrificed mice after one-, three-, and five-times vaccinations for Treg cell staining and re-stimulation assay. The results showed increased Treg cells in systemic immune responses following multiple vaccinations. Moreover, after restimulated with E7-specific peptide, the immune cells from the mice which had one-time vaccination with codon-optimized GM-CSF-secreting cell-based vaccine showed the highest percentages of IFN-γ-secreting CD8+ T cells compared to three- or five-times vaccinations. Taken together, our data suggested that high-dose GM-CSF vaccine combined with multiple vaccinations would not induce the effective antitumor immune responses. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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