State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, Fourth Military Medical University , Xi'an , P. R. China.
Research and Development Department, Jiangsu Pacific Meinuoke Biopharmaceutical Company , Changzhou , 213022 , P. R. China.
Cancer Biol Ther. 2019;20(12):1443-1452. doi: 10.1080/15384047.2019.1647052. Epub 2019 Aug 14.
: Esophageal cancer is a highly aggressive neoplasm. Targeted therapy has been proven to be a promising way for cancer therapy. Here, we report a novel anti-CD147 antibody for esophageal cancer therapy, which is a chimeric antibody with modified glycoform in Fc region. : ADCC assay was used to explore the antitumor efficacy of Metuzumab against esophageal cancer . Wound healing assay and Boyden Chamber invasion assay were performed to explore whether Metuzumab could inhibit migration and invasion of esophageal cancer . Insulin-like growth factors 1 (IGF-1) and PI3k/Akt was assayed for elaborating antagonistic mechanism of Metuzumab in migration and invasion of esophageal cancer cells. Subcutaneous xenograft nude mouse model was used to investigate the antitumor efficacy of Metuzumab against esophageal cancer . The esophageal cancer tissue microarrays (TMA) was examined for identification of association of CD147 with lymph node metastasis, and the footpad xenograft nude mouse model was used to explore whether Metuzumab could inhibit lymph node metastasis of esophageal cancer : The results showed that Metuzumab exhibited higher ADCC compared to the wild type antibody cHAb18. Metuzumab inhibited migration and invasion of esophageal cancer through blockade of CD147 . The results of Western blot showed Metuzumab might inhibit migration and invasion of esophageal cancer cells through suppressing activation of PI3k/Akt and expression of IGF-1. Experiments showed that Metuzumab exhibited significant antitumor efficacy and inhibited lymph node metastasis of esophageal cancer in xenograft models. The immunochemical staining of TMA showed CD147 was high-expressed on various kinds of esophageal cancer tissues and associated with the grade of lymph node-metastasis. : The and study demonstrated dual effects of Metuzumab in effectively mediating ADCC by activating effector cells, and inhibiting metastasis of esophageal cancer through blockade the function of CD147, providing justification for moving Metuzumab forward to clinical development in esophageal cancer.
食管癌是一种高度侵袭性的肿瘤。靶向治疗已被证明是癌症治疗的一种有前途的方法。在这里，我们报告了一种用于食管癌治疗的新型抗 CD147 抗体，它是一种在 Fc 区具有修饰糖型的嵌合抗体。
ADCC 测定用于探索 Metuzumab 对食管癌的抗肿瘤功效。进行划痕愈合试验和 Boyden 室侵袭试验，以探索 Metuzumab 是否可以抑制食管癌的迁移和侵袭。测定胰岛素样生长因子 1（IGF-1）和 PI3k/Akt，以阐述 Metuzumab 在食管癌细胞迁移和侵袭中的拮抗机制。使用皮下异种移植裸鼠模型研究 Metuzumab 对食管癌的抗肿瘤功效。使用食管癌组织微阵列（TMA）检查 CD147 与淋巴结转移的关联，并使用足底异种移植裸鼠模型探索 Metuzumab 是否可以抑制食管癌的淋巴结转移。
结果表明，与野生型抗体 cHAb18 相比，Metuzumab 表现出更高的 ADCC。Metuzumab 通过阻断 CD147 抑制食管癌的迁移和侵袭。Western blot 结果表明，Metuzumab 通过抑制 PI3k/Akt 的激活和 IGF-1 的表达来抑制食管癌细胞的迁移和侵袭。实验表明，Metuzumab 在异种移植模型中表现出显著的抗肿瘤功效并抑制了食管癌的淋巴结转移。TMA 的免疫化学染色显示 CD147 在各种食管癌组织中高表达，并与淋巴结转移的程度相关。
研究表明，Metuzumab 通过激活效应细胞有效介导 ADCC 的双重作用，以及通过阻断 CD147 的功能抑制食管癌的转移，为将 Metuzumab 推进食管癌的临床开发提供了依据。
