| Objective Using phage antibody library display technology and choosing VEGFR - 2 as an antigen, massive purified high-affinity chimeric Fab antibodies can be obtained. cFab can inhibit tumor angiogenesis by competitively inhibiting the combination of VEGF and VEGFR-2. In this study, orthotopic xenograft tumor model of hepatocellular carcinoma was created and the inhibitory effect of a mouse chimeric anti-VEGFR-2 Fab antibody on growth of an orthotopic xenograft tumor of hepatocellular carcinoma was investigated, accompanying with the examination of the antibody on tumor angiogenesis. .Methods Binding activity of cFab antibody was assessed by ELISA. an orthotopic xenograft tumor model of hepatocellular carcinoma was created by injection of H22 cells directly into the liver parenchyma of ICR mice, and twenty-four ICR mice bearing orthotopic HCC were divided into two groups: control group, cFab group. During and after the treatment, the weight, the survival time and the hepatocellular carcinoma specimens of animals were compared between the two groups, and we also stained specimens with hematoxylin/eosin, immunostained tissue sections, and counted microvessel density in H22 solid tumor of the two groups. Results The chimeric anti-VEGFR-2 Fab antibody exhibited a strong binding activity to VEGFR-2. The tumor size in cFab group was significantly decreased compared with control group(313.9±41.9 mm~3 vs 635.4±70.1 mm~3, P<0.05); but the mice in this group had a significantly longer survival time(long-rank testχ~2=4.611,P=0.032), the median time in cFab group was 20.0 and in the control group it was 13.0; In the meantime, the microvessel density in cFab group was also significantly lower than that in control group (34.48±1.39 vs 9.56±1.26, P<0.05).Conclusion The chimeric anti-VEGFR-2 Fab antibody can inhibit the growth of an orthotopic xenograft tumor of hepatocellular carcinoma, and the inhibitory mechanism may be related to the antiangiogenesis activity of cFab antibody.
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