Complement Regulatory Protein CD55 And CD59 Monoclonal Antibody Enhancing Herceptin Efficiency Against Lung Carcinoma Cell Line A549 And H157 And Its Mechanisms

With the increasing exploration on the therapeutic targets of tumor, as well as the development of monoclonal antibody (MAb) technology, the treatment with monoclonal antibodies against tumor have been transferred into clinic from bench. Herceptin, a kind of humanized anti-Her2/neu MAb, is one of clinically being used MAbs. The target of Herceptin is HER2/neu oncogene, a member of the epidermal growth factor receptor (EGFR) family. The amplification and overexpression of HER2/neu oncogene has been observed in many tumors such as breast cancer, ovary cancer, colon cancer, lung cancer, stomach cancer, prostate cancer and cervix cancer, etc. Previous studies showed that there were 5-50% of cases expressing HER-2 in non-small cell lung cancer (NSCLC) patients, and it could be used for prediction of bad prognosis. Herceptin was firstly applied to the treatment of breast cancer successfully and gradually used in solid tumors including NSCLC. However, the efficiency rate of this promising therapeutic MAb is no more than 15% in the treatment of NSCLC, which is possibly due to the partial inhibition of the biological effects of Herceptin after its binding to the tumor cells.Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) are involved in the mechanisms underlying the efficiency of MAb against tumor. The efficiency of CDC against tumor mostly depends on the activation of complement proteins, which are regulated by complement regulatory proteins (CRP). Therefore, the expression and its clinical significance of CRP is increasingly becoming a hotspot when aiming to increase the efficiency of CDC against tumor cells. Based on the importance of CRPs in CDC, we hypothesized that CD55 and CD59, two key CRPs, might be expressed on lung carcinoma cells, thereby partially contribute to the low clinical efficiency of Herceptin. If it is true, can the efficiency of Herceptin be improved with the use of anti-CD55 and anti-CD59 MAb during administration of Herceptin? Furthermore, clinical trials have shown that the clinical efficiency of Herceptin can be significantly...