Carrier cell mediated ovarian cancer specific gene therapy

我们构建了一种溶瘤腺病毒AdE 3-IAI. 3B，其引入了卵巢癌特异性IAI. 3B启动子，并在体外和体内显示了对卵巢癌细胞增殖的生长抑制作用（Cancer Research，2003）。假设AdE 3-IAI. 3B治疗的问题是，即使在治疗后约30天暂时进行肿瘤缩小，所有肿瘤也会在2-3周内复发。这不仅在动物实验中得到证实，而且在使用其他溶瘤载体的临床试验中也得到证实。据推测，这是因为载体在肿瘤内的滞留率小，滞留时间短，载体从肿瘤迅速向全身转移的原因之一。将AdE 3-IAI. 3B感染到作为载体细胞的已知为腺病毒生产细胞的293和A549细胞中，并将这些载体细胞施用到卵巢癌的裸鼠皮下肿瘤模型PA-1和RMG-1细胞中， 关于我们 如果IAI. 3B启动子高，则两个肿瘤完全消失并且没有复发。另一方面，腺病毒受体少于这些细胞的HEY细胞肿瘤在两者一起使用时消失，并且没有复发，尽管在用AdE 3-IAI感染的293或A549细胞进行单细胞治疗后肿瘤并没有消失。3B。众所周知，腺病毒载体的第二次攻击被抗腺病毒抗体的产生完全阻断。而用AdE 3-IAI. 3B感染的293或A549载体细胞进行第二次攻击则获得成功。第二次腺病毒感染的这种恢复被0. 12 μ m的膜室可阻断50%以上。这是由于通过载体细胞与靶细胞的直接接触和载体细胞片段与靶细胞的直接接触实现了感染。电镜证实了溶瘤腺病毒感染载体细胞的这种感染方式。少

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 … More 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