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 or a31I labeled BVE-I, with normal mouse IgG or 131 I 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 microvesse| density (TMVD) recorded.
Results: The inhibition effects of tumor growth 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 the antibody treatment, leading to a decrease in the death rate. This effect was enhanced when treated with 131Ilabeled 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.
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 or a31I labeled BVE-I, with normal mouse IgG or 131 I 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 microvesse| density (TMVD) recorded.
Results: The inhibition effects of tumor growth 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 the antibody treatment, leading to a decrease in the death rate. This effect was enhanced when treated with 131Ilabeled 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.