Construction And Eukaryotic High-level Expression Of Anti-human ErbB2 Mouse/human Chimeric Antibody For Adjuvant Therapy Of Ovarian Carcinoma

Ovarian cancer is still one of the leading causes of mortality among gynecological malignancies. Although some advances have been made in surgical treatment and the cisplatin-based chemotherapy, the five-year survival rate has not yet changed significantly during the past 20 years, only about 30%. The prognosis is very poor because of high incidence of recurrence or metastasis, also related to resistance to conventional drug therapy and lack of early diagnosis. Therefore, it's needed urgently to develop new strategies for treatment of ovarian cancer in order to improve the long term outcome. The immunotherapy will be help to the patients of ovarian cancer. Tumor antigens play an important roles in initiating immuno-response and acting as targets for immuno-attack.erbB2 is a member of a family of epithelial growth factor receptors that interact with each other and various ligands to stimulate various intracelluar signal transduction pathways involved in cell growth control. erbB2 is overexpression in 25%-30% of women with ovarian cancer. Patients with erbB2 overexpression had a significantly lower overall survival rate and a shorter time to relapse than that in patients without overexpress erbB2. The clinical investigation revealed that all the patients with overexpression of erB2 died within 2 years after diagnosis, whereas some ovarian cancer patients without overexpress erbB2 may live up to 15 years after diagnosis. Therefore, erbB2 overexpress seems to play an important role in the pathogenesis and subsequent progression of human ovarian cancers. Activation of the erbB2 receptor signaling pathways can enhance various metastasis-associated properties that lead to an increase of cancer metastasis. Additionally, erbB2 overexpression confers therapeutic resistance via receptor-mediated antiapoptotic signals. To limit these disastrous effects of the overexpressed erbB2, various erbB2-blocking strategies have been tested in clinical trials or approved as therapies for erbB2 overexpressing cancers. The strategies based on antibody have shown great success in this field. The excellent example is Herceptin, a humanized antibody was developed from anti-erbB2 murine monoclonalantibody that also binds to the extracelluar domain of erbB2 and down-regulate the expression of cell-surface erbB2 proteins, which shows good curative effects in metastatic breast cancer. As erbB2 overexpression in ovarian cancer and concern with poor prognosis and drug resistance, we then construction anti-human erbB2 mouse/human chimeric antibody and high-level expressed in CHO cells for adjuvant therapy of ovarain cancer.The study on relationship between the expression of C-erbB2% C-erbB3> C-erbB4 and ovarian cancerTumorous samples were obtained from 49 patients with ovarian cancer, 21 cases of benign tumor and 19 cases of normal controls were detected the expression of C-erbB2> C-erbB3^ C-erbB4 receptor protein by immunohistochemical technique (IHC). The incidence of all 3 proteins with malignant tumors was significantly greater than that in benign or normal tissues(p<0.05). C-erbB2 >. C-erbB3 - C-erbB4 overexpression correlated with increasing FIGO stage. No correlation was found with histological type and differentiation grade. These results show that the expression of C-erbB2^ C-erbB3> C-erbB4 was correlated with the carcinogenesis and progress of ovarian cancer. The positive expression of C-e^bB2^ C-erbB3^ C-erbB4 were observed more frequently in patients with large amount of ascites volume(p<0.05).The levels of C-erbB2^ C-erbB4 in patients with residual disease >2cm than that in those have none(p<0.05). There is a close relationship between the expression C-erbB2 and lymph node metastasis (p<0.05). A tendency towards correlation was found for C-erbB4(p=0.0572). The positive expression rate of C-erbB2s C-erbB3^ C-erbB4 in patients with omentum involvement was significantly higher than that in patients without omentum involvement (p<0.05). It was also found that the expression of C-erbB2 ^ C-erbB4 in patients with re...