Target-specific transport of therapeutic agents holds promise to increase the efficacy of cancer treatment by decreasing injury to normal tissues and post treatment problems. HER2 is a tumor cell surface marker that is expressed in 25-30 % of breast cancer patients. The significant role of HER2 in cancer development and its biological feature makes it a highly appealing goal for the therapeutic treatment of cancer targeted therapy using HER2 monoclonal antibody. This approach is currently used as a special treatment against breast cancer in some research. In the present study, HER2 monoclonal antibody (mAb), (Herceptin) fused to PE38 by recombinant DNA technology and a new recombinant IT was developed. The scFv(Herceptin)-PE-STXA and scFv(Herceptin)-PE fusions cloned in pET28a and recombinant protein expression was carried out and then the proteins were purified. MCF-7 and SKBR-3 cells were used as HER2-negative and HER2-positive breast cancer cells, respectively. The cytotoxicity of its evaluated using MTT assay. The cell ELISA was used to determine the binding ability of immunotoxins (ITs) to the cell receptor and internalization and apoptosis were also assessed. The results revealed that cell cytotoxicity occurred in SKBR-3 cells in a dose-dependent manner but not in MCF-7 cells. It is possible that this ITs can attach to HER2-positive breast cancer cells and then, internalize and eradicate cancer cells by apoptosis. Here, we concluded that the recombinant ITs have therapeutic potential against HER2-positive breast cancer.

中文翻译：

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使用双重和三重融合免疫毒素靶向/治疗乳腺癌。


治疗剂的靶向运输有望通过减少对正常组织的损伤和治疗后问题来提高癌症治疗的功效。 HER2 是一种肿瘤细胞表面标志物，在 25-30% 的乳腺癌患者中表达。 HER2在癌症发展中的重要作用及其生物学特性使其成为利用HER2单克隆抗体进行癌症靶向治疗的极具吸引力的目标。目前，这种方法在一些研究中被用作针对乳腺癌的特殊治疗方法。本研究通过重组DNA技术将HER2单克隆抗体（mAb）（赫赛汀）与PE38融合，开发出一种新的重组IT。将scFv(Herceptin)-PE-STXA和scFv(Herceptin)-PE融合体克隆到pET28a中，进行重组蛋白表达，然后纯化蛋白。 MCF-7和SKBR-3细胞分别用作HER2阴性和HER2阳性乳腺癌细胞。采用MTT法评价其细胞毒性。使用细胞 ELISA 测定免疫毒素 (IT) 与细胞受体的结合能力，并评估内化和细胞凋亡。结果表明，细胞毒性在SKBR-3细胞中以剂量依赖性方式发生，而在MCF-7细胞中则不然。这种 IT 可能会附着在 HER2 阳性乳腺癌细胞上，然后通过细胞凋亡将癌细胞内在化并消灭。在此，我们得出结论，重组 IT 具有治疗 HER2 阳性乳腺癌的潜力。