Metuzumab Inhibits Proliferation And Metastasis Of Esophagus Cancer Cells In Vitro And In Vivo

Esophageal cancer is a highly aggressive neoplasm, which is the sixth leading cause of cancer death worldwide. According to the data released by the World Health Organization, more than 40 million people died of esophageal cancer each year. Unfortunately, China is a high-incidence country for esophageal cancer. Surgery, in conjunction with radiation and chemotherapy, is the major treatment for esophageal cancer. However, the 5-year overall survival rate(14%) remains poor. High rate of tumor recurrence and lymph node metastasis poses a great threat to patients. In recent years, targeted therapies brought hope for patients with esophageal cancer. It has been reported that cetuximab, trastuzumab and bevacizumab have encouraging effects on esophageal cancer.Previous studies have shown that HAb18G/CD147 plays an important role in tumor progression, and the molecule is highly-expressed on kinds of tumors including esophagus cancer. Our center has developed a new CD147-targeting antibody, Metuzumab(HcHAb18). On one hand, Metuzumab binds to tumor cells specifically, inhibits migration and invasion through blockade of HAb18G/CD147. On the other hand, Metuzumab has a stronger antibody-dependent cell mediated cytotoxicity(ADCC) effect compared with the parental antibody, because of a higher affinity with activating Fc receptor(FcγRIIIA) on NK cells. AimTo explore the efficacy of Metuzumab on inhibiting growth and metastasis of esophageal cancer cells in vitro and in vivo. Methods1. We use an ADCC assay to explore the cytotoxicity of Metuzumab on esophageal cancer in vitro. We built subcutaneous xenograft nude mouse model to explore the antitumor efficacy of HcHAb18 against esophageal cancer in vivo. 2. We explored whether HcHAb18 inhibits the invasion and metastasis of esophageal cancer, using transwell and wound healing assay. We further built footpad xenograft nude mouse model to explore whether HcHAb18 inhibits lymphatic metastasis of esophageal cancer in vivo. ResultsMetuzumab(HcHAb18) mediated enhanced ADCC against esophageal cancer(62%), and exhibited significant, dose-dependent antitumor efficacy in subcutaneous xenograft models(72.5%). However, Metuzumab alone did not inhibit proliferation or induce apoptosis of esophageal cancer cells. Metuzumab inhibited invasion and migration of esophageal cancer cells in vitro. Metuzumab inhibited distant lymphatic metastasis in footpad xenograft model. ConclusionThe results indicate that Metuzumab(HcHAb18) exhibited enhanced ADCC against esophageal cancer in vitro and in vivo. Metuzumab inhibits migration, invasion and distant lymphatic metastasis of esophageal cancer through blockade of HAb18G/CD147. Thus, Metuzumab can be a targeted therapy drug against esophageal cancer in the future.