https://scholars.lib.ntu.edu.tw/handle/123456789/309883
Title: | Curative Potential of GM-CSF-Secreting Tumor Cell Vaccines on Established Orthotopic Liver Tumors: Mechanisms for the Superior Antitumor Activity of Live Tumor Cell Vaccines | Authors: | Tai, Kuo-Feng DING-SHINN CHEN Hwang, Lih-Hwa |
Keywords: | Granulocyte-macrophage colony-stimulating factor (GM-CSF); Irradiated vaccine; Live vaccine; Orthotopic liver tumor; Tumor cell vaccine | Issue Date: | 2004 | Journal Volume: | 11 | Journal Issue: | 2 | Start page/Pages: | 228-238 | Source: | Journal of Biomedical Science | Abstract: | In preclinical studies, tumor cells genetically engineered to secrete cytokines, hereafter referred to as tumor cell vaccines, can often generate systemic antitumor immunity. This study investigated the therapeutic effects of live or irradiated tumor cell vaccines that secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) on established orthotopic liver tumors. Experimental results indicated that two doses (3 × 107 cells per dose) of irradiated tumor cell vaccines were therapeutically ineffective, whereas one dose (3 × 106 cells) of live tumor cell vaccines caused complete tumor regression. In vivo depletion of CD8+ T cells, but not natural killer cells, restored tumor formation in the live vaccine-treated animals. Additionally, the treatment of cells with live vaccine induced markedly higher levels of cytotoxic T lymphocyte activity than the irradiated vaccines in the draining lymph nodes. The higher levels of cytokine and antigen loads could partly explain the superior antitumor activity of live tumor cell vaccines, but other unidentified mechanisms could also play a role in the early T cell activation in the lymph nodes. A protocol using multiple and higher dosages of irradiated tumor cell vaccines also caused significant regression of liver tumors. These results suggest that the GM-CSF-secreting tumor cell vaccines are highly promising for orthotopic liver tumors if higher levels of immune responses are elicited during early tumor development. Copyright ? 2004 National Science Council, ROC and S. Karger AG, Basel. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-1442328755&doi=10.1159%2f000076035&partnerID=40&md5=53d49084790651955f7eed5537e0b222 http://scholars.lib.ntu.edu.tw/handle/123456789/309883 |
DOI: | 10.1159/000076035 | SDG/Keyword: | granulocyte macrophage colony stimulating factor; live vaccine; tumor cell vaccine; animal cell; antineoplastic activity; article; cancer radiotherapy; controlled study; drug effect; drug mechanism; immune response; in vivo study; irradiation; liver tumor; lymph node; nonhuman; priority journal; rat; T lymphocyte; T lymphocyte activation; tumor cell; tumor regression; Animals; Cancer Vaccines; CD8-Positive T-Lymphocytes; Cell Line, Transformed; Cell Transplantation; Cytotoxicity Tests, Immunologic; Granulocyte-Macrophage Colony-Stimulating Factor; Killer Cells, Natural; Liver Neoplasms, Experimental; Rats; Rats, Inbred F344; T-Lymphocytes, Cytotoxic; Treatment Outcome; Animalia |
Appears in Collections: | 醫學系 |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.