Anti-Tumor Effects and Mechanisms of the Fully Human anti-EGFR Monoclonal Antibody (Ranti-HER)
PAN Dong-sheng1, SHEN Lian-zhong2, GAI Wen-lin3, ZHOU Xiao-bing1, LI Bo1*
1. Beijing Key Laboratory, Beijing, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing 100176, China; 2. Shandong Xinbo Pharmaceutical R&D, Ltd, Dezhou 251500, China; 3. Cell Engineering Research Center, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100176, China
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 Anti-tumor 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.
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PAN Dong-sheng, SHEN Lian-zhong, GAI Wen-lin, ZHOU Xiao-bing, LI Bo. Anti-Tumor Effects and Mechanisms of the Fully Human anti-EGFR Monoclonal Antibody (Ranti-HER). Chinese Pharmaceutical Journal, 2016, 51(21): 1839-1847.
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2016, Vol. 51 
