摘要：

The HER2 receptor is overexpressed in 20-30% of breast cancers. HER2 overexpression in breast cancer has been successfully targeted by both antibody and antibody-drug conjugate approaches. Trastuzumab, a humanized monoclonal antibody is approved for the treatment of HER2 positive metastatic breast cancer. More recently, trastuzumab-DM1, an antibody drug conjugate (ADC), has shown promising clinical results in patients refractory to trastuzumab. Because DM1 is a chemotherapeutic and refractory breast cancer patients have typically progressed through several rounds of chemotherapy, we were interested in developing a new ADC approach with trastuzumab that utilized a novel mechanism of action. 5G2 is an engineered toxin body comprised of the trastuzumab scFv and a modified ribosome-inhibiting protein derived from Shiga-like toxin 1 A. 5G2 has exhibited high binding affinity to HER2 protein and HER2-expressing cells. 5G2 exerts a potent HER2-specific cytotoxic effect on HER2-expressing cells, but little activity on various HER2 negative cells. These results demonstrate that 5G2 is a promising HER2-targeted therapeutic agent against breast carcinomas and is currently under further development.

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