Anti-tumor angiogenesis with a recombinant ag43/FGFR1 chimeric protein as a model antigen

Abstract

In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein (AF) vaccine in a mouse H22 hepatoma model, tumor volume and survival rate of the mice were studied at a 3-day interval. Microvessel density (MVD) was detected by immunohistochemistry. The endothelial deposition of autoantibodies within tumor tissues was examined by immunofluorescent staining, and anti-FGFR1 antibody-producing B cells (APBCs) were tested by enzyme-linked immunospot (ELISPOT) assay. Compared with the three control groups, the tumor volume was significantly decreased and the survival time was significantly prolonged in AF-immunized group (P<0.05). The number of APBCs in AF-immunized mice (129.6±10.9) was more than in controls [6.2±1.1 (FGFR1), 6.0±1.2 (Ag43) and 5.2±1.4 (NS), P<0.01]. Moreover, the endothelial deposition of autoantibodies was found in tumor tissues from AF-immunized mice, but not in control groups. MVD in AF-immunized group was significantly lower than in FGFR1-immunized group, Ag43-immunized group and NS group (10.3±3.1 vs 39.4±8.6 vs 42.3±9.8 and 43.6±10.6, P<0.01). These findings demonstrated that the AF protein vaccine effectively inhibited tumor angiogenesis and growth via production of autoantibodies against self-FGFR1.

Keywords

fibroblast growth factor receptor-1 / antigen 43 / angiogenesis / immunotherapy

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