Anti-tumor effects and mechanisms of the fully human anti-EGFR monoclonal antibody (Ranti-HER) / 中国药学杂志

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.