| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
We constructed an oncolytic adenovirus, AdE3-IAI.3B that was introduced ovarian cancer specific IAI.3B promoter, and showed the effect of the growth inhibition in the ovarian cancer cell proliferation in vitro and in vivo (Cancer Research, 2003). The treatment by AdE3-IAI.3B is assumed the problem that all tumors relapses in 2-3 weeks further even if tumor reduction is temporarily done on about 30 days after the treatment. This is confirmed not only in the animal experiment but also in the clinical trial by using other oncolytic vectors. It is guessed that it is a cause that vector rapidly shifts to the whole body from the tumor, because the stagnation rate of vector in the tumor is few, and the stagnation time in the tumor is short. After AdE3-IAI.3B had been infected to 293 and A549 cells that had been known as an adenoviral production cell so far as a carrier cell and these carrier cells were adminstered to the nude mouse subcutaneous tumor model of ovarian cancer PA-1 and RMG-1 cel
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l that the IAI.3B promoter is high, both tumors completely disappeared and did not relapsed. On the other hand, the HEY cell tumor, whose adenoviral receptor is fewer than these cells, disappeared and the relapse was not admitted when both were used together, though the tumor did not disappear after the single cell treatment by 293 or A549 cells infected with AdE3-IAI.3B. It is well known that the second challenge of adenoviral vectors is completely blocked by the anti-adenoviral antibody production. However, the second challenge of adenovirus succeeded by using AdE3-IAI.3B infected 293 or A549 carrier cell. This restoration of the second adenoviral infection was completely blocked by 0. 4 um millicell membrane chamber and 50% blocked by 12 um millicell memebrane chamber. This was due to the infection achievement by direct carrier cell to target cell contact and carrier cell fragment to target cell contact. This infection style of oncoloytic adenovirus infected carrier cell was confirmed by the electron microscope. Less
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