Antitumor effect of an anti-endothelial cell monoclonal antibody BVE-1 on solid tumor xenograft in nude mice

Abstract

Objective: To study the possibility of treatment for solid tumors by targeting vascular endothelial cells with a monoclonal antibody (MoAb) BVE-1. Methods: Leiomyosarcoma cell line SK-LMS-1, liver cancer cell line 7721 and pancreatic cancer cell line SW1990 xenografts in nude mice were treated ip with an antiendothelial cell monoclonal antibody BVE-1 or131I labeled BVE-1, with normal mouse IgG or131I labeled IgG as controls. The tumor volume was measured at regular intervals following treatment. After sacrificing of the mice, the tumors were histologically examined and the intra-tumoral microvessel density (TMVD) recorded. Results: The inhibition effects of tumor growth in mice treated with BVE-1 were 49.8% in SK-LMS-1, 48.7% in SW1990 and 70.5 in 7721 respectively. Metastasis of leiomyosarcoma was also inhibited by the antibody treatment, leading to a decrease in the death rate. This effect was enhanced when treated with131I-labeled BVE-1 as the inhibition rate of tumor growth increased to 82.2–86.6%. Pathologically, vascular endothelial cells degeneration, occlusion of blood vessels and massive tumor cells necrosis around the degenerated vessels were observed in the BVE-1 treated mice. TMVD was significantly lower in the BVE-1 treated mice than that in mice treated with normal mouse IgG and in the untreated mice. Conclusion: The monoclonal antibody against vascular endothelial cells BVE-1 is effective in the treatment of human cancer xeno-grafted in nude mice by the induction of vascular endothelial degeneration and vascular occlusion inside the tumor. It may be used as a novel strategic approach in the treatment of human solid tumors.