Deshane J, Grim J, Loechel S, Siegal G P, Alvarez R D, Curiel D T
Gene Therapy Program, University of Alabama, Birmingham 35294, USA.
Cancer Gene Ther. 1996 Mar-Apr;3(2):89-98.
Methods were developed to achieve targeted eradication of the erbB-2 oncoprotein using gene constructs encoding anti-erbB-2 intracellular single-chain antibodies. This method of genetic intervention caused a marked cytocidal effect in erbB-2-overexpressing human ovarian tumor cells. Evaluation of the mechanistic basis of this phenomenon demonstrated that programmed cell death had been induced. Significantly, no cytocidal effect was observed in non-erbB-2-overexpressing tumors. The induction of apoptosis could be shown to be secondary to the intracellular antibody-mediated ectopic localization of the erbB-2 oncoprotein. Thus, the strategy of selective oncogene "knock-out" using intracellular antibodies represents a novel anticancer gene therapy strategy that offers the potential to achieve highly specific, targeted eradication of human tumor cells.
利用编码抗erbB-2细胞内单链抗体的基因构建体，开发出了实现erbB-2癌蛋白靶向根除的方法。这种基因干预方法在erbB-2过表达的人卵巢肿瘤细胞中引起了显著的细胞杀伤作用。对这一现象的机制基础进行评估表明，已诱导了程序性细胞死亡。值得注意的是，在非erbB-2过表达的肿瘤中未观察到细胞杀伤作用。凋亡的诱导可证明是细胞内抗体介导的erbB-2癌蛋白异位定位的结果。因此，使用细胞内抗体进行选择性癌基因“敲除”的策略代表了一种新型抗癌基因治疗策略，具有实现高度特异性、靶向根除人类肿瘤细胞的潜力。
