The effects of combined interleukin-12- and interleukin-18-based immunogene therapy and anti-angiogenesis gene therapy on gliomas in rats
Date Issued
2005-07-31
Date
2005-07-31
Author(s)
曾勝弘
DOI
932314B002043
Abstract
This 3-year project is intended to investigate the effects of combined
granulocyte-macrophage colony-stimulating factor (GM-CSF)-, interleukin-12 (IL-12)- and
IL-18-based gene therapy and anti-angiogenesis gene therapy on the intracerebral gliomas in rats.
In the first year, we constructed several recombinant adenoviral vectors, including Ad/IL-12,
Ad/IL-18, Ad/Endo, Ad/G+E with the titers in the range of 1011 to 1012 pfu. Then these adenoviral
vectors were used to treat the intracerebral gliomas. All the control rats and the rats treated with
Ad/IL-18 died. By contrast, the survival rate of the rats treated with Ad/IL-12 was 50%, Ad/ME
was 30%, Ad/IL-12+Ad/IL-18 was 50%, Ad/IL-12+Ad/ME was 70%, Ad/IL-18+Ad/ME was
30%, and Ad/IL-12+Ad/IL-18+Ad/ME was 70%. The Ad/IL-12, Ad/IL-12+Ad/IL-18,
Ad/IL-12+Ad/ME, and Ad/IL-12+Ad/IL-18+Ad/ME groups had higher survival rate than the
control groups (P<0.05). However, the Ad/IL-18, Ad/ME, Ad/IL-18+ Ad/ME groups showed no
significant difference from the control groups (P>0.05). on the other hand,
Ad/IL-12+Ad/IL-18+Ad/ME group had higher survival rate than Ad/IL-18, Ad/ME, or
Ad/IL-18+Ad/ME groups (P<0.05), but showed no difference from the Ad/IL-12,
Ad/IL-12+Ad/IL-18, or Ad/IL-12+Ad/ME groups (P>0.05). The results indicated that Ad/IL-12
alone was effective for the treatment of intracerebral gliomas, by contrast, Ad/IL-18 had no
therapeutic effect on the glioma. Combined Ad/IL-12 and Ad/IL-18 showed no synergistic effects.
Combined Ad/IL-12 and Ad/ME shoed synergistic effects on the intracerebral gliomas, however,
addition of Ad/IL-18 did not enhance the therapeutic effects. In the second year, we modified the
strategies and included the adenoviral vector carrying granulocyte-macrophage
colony-stimulating factor (GM-CSF) and endostatin (Ad/G+E) in the treatment methods. We
found that the survival rate of the rats treated with Ad/G+E was 50%, Ad/IL-12+Ad/G+E was
60%, Ad/IL-18+Ad/G+E組 was 50%, Ad/IL-18+Ad/IL-12+Ad/G+E was 80%. The survival rate
of these groups was significantly higher than that of the control group (P<0.05); however, was not
different from that of the groups treated with Ad/IL-12, Ad/IL-12+Ad/IL-18, Ad/IL-12+Ad/ME,
Ad/IL-12+Ad/IL-18+Ad/ME (P>0.05). By contrast, the survival rate of the group treated with
Ad/IL-18+Ad/IL-12+Ad/G+E was higher than that of the group treated with Ad/IL-18+Ad/ME
(P=0.03). Furthermore, the survival time of the group treated with Ad/IL-18+Ad/IL-12+Ad/G+E
was longer than that of all tested groups (P<0.05) except the group treated with
Ad/IL-12+Ad/IL-18+Ad/ME. The results suggested that combination of GM-CSF, IL-12, and
IL-18-based immunogene therapy and the anti-angiogenesis therapy had synergistic therapeutic
effects on gliomas.
Subjects
glioma
immunogene therapy
anti-angiogenesis gene therapy
granulocyte-macrophage colony-stimulating factor
adenoviral vector
Publisher
臺北市：國立臺灣大學醫學院外科
Type
report
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