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

Objective: To study the possibility of treatment forsolid tumors by targeting vascular endothelial cells witha monoclonal antibody (MoAb) BVE-1. Methods:Leiomyosarcoma cell line SK-LMS-1, liver cancer cellline 7721 and pancreatic cancer cell line SW1990xenografts in nude mice were treated lp with an antiendothelial cell monoclonal antibody BVE-1 or 13iflabeled BVE-1, with normal mouse IgG or 131 1 labeledIgG as controls. The tumor volume was measured atregular intervals following treatment. After sacrificingof the mice, the tumors were histologically examinedand the intra-tumoral microvessel density (TMVD)recorded. Results: The inhibition effects of tumorgrowth in mice treated with BVE-1 were 49.8% in SKLMS-1, 48.7% in SW1990 and 70.5 in 7721 respectively.Metastasis of leiomyosarcoma was also inhibited by theantibody treatment, leading to a decrease in the deathrate. This effect was enhanced when treated with 131I-labeled BVE-1 as the inhibition rate of tumor growthincreased to 82.2-86.6%. Pathologically, vascularendothelial cells degeneration, occlusion of blood vesselsand massive tumor cells necrosis around thedegenerated vessels were observed in the BVE-1 treatedmice. TMVD was significantly lower in the BVE-1treated mice than that in mice treated with normalmouse IgG and in the untreated mice. Conclusion: Themonoclonal antibody against vascular endothelial cellsBVE-1 is effective in the treatment of human cancerxeno-grafted in nude mice by the induction of vascularendothelial degeneration and vascular occlusion insidethe tumor. It may be used as a novel strategic approachin the treatment of human solid tumors.