https://scholars.lib.ntu.edu.tw/handle/123456789/476186
標題: | Induction of T-cell apoptosis in rats by genetically engineered glioma cells expressing granulocyte-macrophage colony-stimulating factor and B7.1 | 作者: | SHENG-HONG TSENG Chen Y. Chang C.-J. Tai K.-F. Lin S.-M. Hwang L.-H. |
公開日期: | 2005 | 卷: | 11 | 期: | 4 | 起(迄)頁: | 1639-1649 | 來源出版物: | Clinical Cancer Research | 摘要: | Purpose: To evaluate antitumor effects on intracerebral gliomas of genetically engineered tumor vaccines expressing granulocyte-macrophage colony-stimulating factor (GM-CSF), B7.1, or both (combination). Experimental Design: A rat glioma cell line, RT-2, was engineered with a retroviral vector to express GM-CSF, B7.1, or combination. Tumorigenicity of engineered cells and therapeutic effects of s.c. given irradiated or live tumor vaccines on parental intracerebral gliomas were studied. Immune cell infiltration induced at vaccine and tumor sites was examined by histologic and immunohistochemical staining. Apoptosis of T cells from vaccine sites was analyzed with fluorescence-activated cell sorting. Results: Engineered RT-2 cells exhibited reduced s.c. tumorigenicity in rats with reduced tumor growth and prolonged animal survival time compared with control rats. Rats with intracerebral gliomas s.c. treated with irradiated or live GM-CSF-expressing vaccines had 60% and 100% survival rates, respectively, significantly better than the control groups (P < 0.05). In contrast, rats treated with vaccines expressing B7.1 or the combination had no or mild therapeutic effects. Studies revealed less T-cell infiltration at both vaccine and tumor sites in rats treated with vaccines expressing B7.1 or the combination than in rats treated with a vaccine expressing GM-CSF. Cell sorting analyses revealed higher proportions of apoptotic T cells at vaccine sites of rats treated with the combination than those treated with vaccine expressing GM-CSF. Conclusions: Combination of GM-CSF- and B7.1-expressing tumor vaccines exerted no synergistic, or even worse, therapeutic effects on gliomas compared with single GM-CSF-secreting tumor vaccine. The worse therapeutic effects of the GM-B7.1-expressing tumor vaccine than the GM-CSF-expressing tumor vaccine were related to the reduced T-cell amount and increased T-cell apoptosis in the former. ? 2005 American Association for Cancer Research. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-14644437735&doi=10.1158%2f1078-0432.CCR-04-1366&partnerID=40&md5=ef9539cb715b19e18a1d5abd50b80cf0 https://scholars.lib.ntu.edu.tw/handle/123456789/476186 |
ISSN: | 1078-0432 | DOI: | 10.1158/1078-0432.CCR-04-1366 | SDG/關鍵字: | B7 antigen; B7.1 antigen; granulocyte macrophage colony stimulating factor; retrovirus vector; tumor vaccine; unclassified drug; animal cell; animal model; animal tissue; antineoplastic activity; apoptosis; article; cancer cell culture; carcinogenicity; cell selection; cell strain RT 2; controlled study; drug effect; fluorescence activated cell sorting; gene expression; genetic engineering; glioma cell; histology; immunohistochemistry; lymphocytic infiltration; nonhuman; priority journal; rat; survival time; T lymphocyte; tumor growth; virus recombinant; Animals; Antigens, CD80; Apoptosis; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cytotoxicity, Immunologic; Flow Cytometry; Genetic Vectors; Glioma; Granulocyte-Macrophage Colony-Stimulating Factor; Rats; Retroviridae; Survival Analysis; T-Lymphocytes; Time Factors; Transfection |
顯示於: | 醫學系 |
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