[Experimental study of the therapeutic effects of an anti-endothelial cell monoclonal antibody BVE-1 for solid tumor xenograft in nude mice].
OBJECTIVE
To study the possibility of targeting endothelial cells with monoclonal antibody for the therapy of 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 i.p. with an anti-endothelial cell monoclonal antibody BVE-1 or 131I labeled BVE-1, with normal mouse IgG or 131I labeled IgG as controls. The tumor volume was measured at regular intervals following treatment. After sacrifice of the mice, the tumor was histologically examined and the intra-tumoral microvessel density(TMVD) recorded.


RESULTS
The tumor growth inhibition effects in mice treated with BVE-1 was 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 decreased death rate. This effect was enhanced when treated with 131I-labeled BVE-1 with an increase of tumor growth inhibition rate to 82.2%-86.6%. Pathologically, capillary endothelial cells degeneration, occlusion of capillaries 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.


CONCLUSIONS
The monoclonal antibody against vascular endothelial cells BVE-1 is effective in the treatment of human cancer xeno-transplanted in nude mice through the induction of capillary endothelial degeneration and vascular occlusion inside of the tumor. It can be used as a novel strategic approach in the treatment of human solid tumors.
Li
P
P
General Hospital of PLA, Beijing.
Yuan
M
M
Xia
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007890:Leiomyosarcoma / Q000473:pathology / Q000628:therapy*; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal