ABSTRACT
OBJECTIVE: To observe the in vivo activity of Ranti-HER, a fully human monoclonal antibody, and combined with the doxorubicin or CPT-11 in established human tumor xenografts in nude mice, and to investigate whether EGFR expression is correlated with this activity. METHODS: The overall receptor of EGF was quantified by flow cytometry. The anti-tumor effects of Ranti-HER were evaluated using established, s /c human carcinoma xenografts in nude mice, and the relative growth rate of tumor was used to assess the anti-tumor activity. RESULTS: A431 cells showed highly expression of EGFR by flow cytometry, SW620 showed negative expression, and EGFR were expressed positively in HT29 and SW948 cells, but both of them were showed low expression. Ranti-HER(0.25-1.0 mg) could inhibit the tumor growth in human A431 epidermoid carcinoma xenografts and dose-effect relationship was observed; Ranti-HER(1.0 mg) could also inhibit the tumor growth in human SW948 colon carcinoma xenografts, but no anti-tumor effects of Ranti-HER 1.0 mg were observed in human HT29 and SW620 colon carcinoma xenografts. Therapeutic enhancement was observed in the A431 xenografts after treatment with Ranti-HER combined with doxorubicin. For another combination regimens, Ranti-HER and CPT-11 proved to be significantly more efficacious than Ranti-HER monotherpy in SW948 xenografts. CONCLUSION: Antitumor activity of Ranti-HER are observed in xenografts in athymic nude mice, and the activity of Ranti-HER is correlated with the EGFR expression; synergistic effects are observed when Ranti-HER is combined with chemicals compared to Ranti-HER monotherapy.
ABSTRACT
@#This study was focus on the optimizing cell culture process of recombinant DG44 cells which expressing novel fully human anti-VEGF165 monoclonal antibody(HVAB). Feed-batch culture and two-phase temperature control were studied for optimizing the HVAB productivity in shaken flasks. The influences of pH changes were determined to study the growth of DG44 cell and expression of HVAB in bioreactors. The HVAB productivity was rose from 101 mg/L to 654 mg/L after feed-batch culture in shaken flask, and cell viability maintained above 80% after reduce the temperature in middle growth phase. It is also suggested that pH range at 6. 4-7. 4 is beneficial to DG44 cells growth and HVAB expression. The productivity in bioreactor is 526 mg/L decreased 11% compare with in shaken flask, which laid an foundation for further pilot scale production.