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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-3-27
pubmed:abstractText
The combined therapeutic effect of cytokine-producing cancer cell vaccines and local radiotherapy was studied in a mouse glioma 261 (GI261) brain tumor model. Brain tumor-bearing mice were treated with cytokine (IL -4, IL-6, IL-7, GM-CSF, TNF-alpha, LIF, LT) producing vaccines made by in vitro transduction of GI261 cells with the corresponding adenoviral vectors. Vaccines producing either IL-4 or GM-CSF cured 20-40% of mice. The antitumor effect strongly depended on the secreted cytokine level. Vaccination therapy induced specific activation of cytotoxic T lymphocytes measured by cell-mediated cytotoxicity assay. Brain tumors were heavily infiltrated by CD4+ lymphocytes after treatment with IL-4- or GM-CSF-secreting cells. GM-CSF vaccination induced moderate CD8+ infiltration, as well. Depleting either CD4+ or CD8+ lymphocyte subsets abolished the anticancer effect of GM-CSF-expressing cells. Strong synergism was observed by combining cytokine vaccination (GM-CSF, IL-4, IL-12) with local tumor irradiation: about 80-100% of the glioma-bearing mice was cured. The high efficiency of combined treatment was maintained even under suboptimal conditions when neither of the modalities cured any of the mice alone. This suggests that vaccination therapy might open a new potential in the clinical treatment of high-grade gliomas when applied as adjuvant to existing treatment modalities.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0929-1903
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
44-52
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11916244-Adenoviridae, pubmed-meshheading:11916244-Animals, pubmed-meshheading:11916244-Brain Neoplasms, pubmed-meshheading:11916244-CD4-Positive T-Lymphocytes, pubmed-meshheading:11916244-CD8-Positive T-Lymphocytes, pubmed-meshheading:11916244-Cancer Vaccines, pubmed-meshheading:11916244-Combined Modality Therapy, pubmed-meshheading:11916244-Cytotoxicity, Immunologic, pubmed-meshheading:11916244-Genetic Vectors, pubmed-meshheading:11916244-Glioma, pubmed-meshheading:11916244-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:11916244-Interleukin-4, pubmed-meshheading:11916244-Lymphocyte Activation, pubmed-meshheading:11916244-Mice, pubmed-meshheading:11916244-Mice, Inbred C57BL, pubmed-meshheading:11916244-Transfection, pubmed-meshheading:11916244-Tumor Necrosis Factor-alpha, pubmed-meshheading:11916244-Vaccination
pubmed:year
2002
pubmed:articleTitle
Local tumor irradiation augments the antitumor effect of cytokine-producing autologous cancer cell vaccines in a murine glioma model.
pubmed:affiliation
Department of Molecular and Tumor Radiobiology, National Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't