https://scholars.lib.ntu.edu.tw/handle/123456789/476219
Title: | Induction of antitumor immunity by intracerebrally implanted rat c6 glioma cells genetically engineered to secrete cytokines | Authors: | SHENG-HONG TSENG Hwang L.-H. Lin S.-M. |
Keywords: | Glioma; GM-CSF; IL-2; IL-4; Tumorigenicity | Issue Date: | 1997 | Journal Volume: | 20 | Journal Issue: | 5 | Start page/Pages: | 334-342 | Source: | Journal of Immunotherapy | Abstract: | To test whether cytokine gene therapy can be applied to an immunologically privileged site, such as the brain, we investigated antitumor immunity in the brain induced by cytokine-secreting glioma cells. Three cytokine genes, interleukin-2 (IL-2), interleukin-4 (IL-4), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were transduced into a rat C6 glioma cell line via a retroviral vector, S2. Rats intracerebrally (IC) implanted with the C6 cells genetically engineered to secrete the cytokines, especially GM-CSF, manifested significantly higher survival rates than those with C6 cells or with C6 cells bearing the control vector (p < 0.002). In vivo, C6 tumors bearing the cytokine genes grew more slowly than wild-type tumors at any time point, and eventually diminished within 6 weeks after tumor cell implantation. Histopathological and immunohistochemical studies revealed that different cytokines induced diverse immune reactions. In the IL-2 group, CD4+ and CD8+ T cells dominated from day 3 to week 4, but disappeared at week 6. Some granulocytes were noted between weeks 2 and 4. In the IL-4 group, eosinophils were noted from day 3 to week 4, and CD4+ and CD8+ T cells, as well as macrophages at week 2. At week 6, only residual levels of macrophages and CD8+ T cells remained. In the GM-CSF group, granulocytes appeared as early as day 1 post-IC tumor implantation, and macrophages at day 2. CD4+ and CD8+ T cells were found from day 3 to week 4. At week 6, only residual CD4+ T cells and macrophages remained. Long-lasting antitumor immunity was confirmed in all groups by rechallenging surviving rats with wild-type C6 cells in the brain 100 days after implanting cytokine gene-bearing C6 cells. In vivo depletion of GM-CSF by anti-GM-CSF antibody further confirmed that the immune reaction induced by GM-CSF-secreting tumor cells were mainly from the action of GM-CSF, rather than the immunogenicity of C6 cells. ? 1997 Lippincott-Raven Publishers. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0031434207&doi=10.1097%2f00002371-199709000-00002&partnerID=40&md5=a385a8a5d799760b1b99903d271997c7 https://scholars.lib.ntu.edu.tw/handle/123456789/476219 |
ISSN: | 1524-9557 | DOI: | 10.1097/00002371-199709000-00002 | SDG/Keyword: | cytokine; granulocyte macrophage colony stimulating factor; interleukin 2; interleukin 4; virus vector; animal cell; animal experiment; animal model; article; cancer transplantation; controlled study; cytotoxic T lymphocyte; eosinophil; gene therapy; genetic engineering; genetic transduction; glioma cell; helper cell; immunohistochemistry; immunotherapy; macrophage; nonhuman; priority journal; rat; tumor immunity |
Appears in Collections: | 醫學系 |
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