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

在日本，肺癌是主要的死亡原因。在许多细胞性肺癌患者中发现表皮生长因子(EGFR)信号的异常，导致细胞生长失控，从而导致肺癌。肺癌患者最初对这些抗癌药反应良好，但随着时间的推移，他们对这些药物产生了获得性耐药性。因此，科学家们继续寻找具有更好活性的新的活性抗癌药物。在本研究中，我们发现抗EGFR的抗体被整合到显示EGFR基因突变的PC-9肺癌细胞中，而不整合到显示正常类型EGFR的PC-14细胞中。然后，我们将抗癌药物(紫杉醇和柔红霉素)连接到抗EGFR抗体上。该偶联抗体对PC-9和PC-14细胞具有相似的细胞毒作用，但活性低于未偶联的抗癌药物。

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.