Anti-cancer antibody targeting epidermal growth factor receptor with constitutively active mutations

肺癌是日本的主要死亡原因。表皮生长因子（epidermal growth factor，EGFR）信号转导异常是导致肺癌发生的重要原因，近年来，针对EGFR酪氨酸激酶的抗肿瘤药物吉非替尼（gefitinib）和厄洛替尼（erlotinib）相继问世。肺癌患者最初对这些抗癌药物反应良好，但随着时间的推移，他们对这些药物产生了获得性耐药性。本研究中，我们发现抗EGFR抗体可掺入EGFR基因突变的PC-9肺癌细胞中，而不能掺入EGFR基因正常的PC-14细胞中。然后，我们将抗癌剂（紫杉醇和柔红霉素）缀合至抗EGFR抗体。偶联抗体对PC-9和PC-14细胞显示出相似的细胞毒性作用，并且其显示出比未偶联的抗癌剂更低的活性。

Lung cancer is the leading cause of death in Japan. Aberrant signaling by epidermal growth factor (EGFR) is found in many cell lung cancer patients, and it leads to uncontrolled cell growth resulting in lung cancer.Recently, anti-cancer agents (gefitinib and erlotinib) targeting EGFR tyrosine kinases were introduced. Lung cancer patients initially respond well to these anti-cancer agents, but they develop acquired resistance to the agents over time. Therefore, scientists continue to search for new active anticancer agents with better activity.In this study, we found that antibody against EGFR is incorporated into PC-9 lung cancer cells which display a mutation within the EGFR gene, but not into PC-14 cells which display normal type of EGFR. Then, we conjugated anti-cancer agents (paclitaxel and daunorubicin) to the anti-EGFR antibody. The conjugated antibody showed similar cytotoxic effcts on PC-9 and PC-14 cells and it shows less activity than unconjugated anti-cancer agents.