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Induction of T-Cell Apoptosis in Rats by Genetically Engineered Glioma Cells Expressing Granulocyte-Macrophage Colony-Stimulating Factor and B7.1
Purpose: To evaluate antitumor effects on intracerebral gliomas of genetically engineered tumor vaccines expressing granulocyte-macrophage colony-timulating factor (GM-CSF), B7.1, or both (combination). Experimental Design: A rat glioma cell line, RT-2, was engineered with a retroviral vector to exp...
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Published in: | Clinical cancer research 2005-02, Vol.11 (4), p.1639-1649 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
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Online Access: | Get full text |
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Summary: | Purpose: To evaluate antitumor effects on intracerebral gliomas of genetically engineered tumor vaccines expressing granulocyte-macrophage
colony-timulating 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. |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-04-1366 |