Anti-tumor angiogenesis with a recombinant ag43/FGFR1 chimeric protein as a model antigen.
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.
Department of Ultrasonography, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. zhengsp528@yahoo.com.cn
Shaoping
S
Zheng
Zhihong
Z
Weng
Shaojiang
S
Zheng
Junli
J
Guo
Fengying
F
Huang
Mingxing
M
Xie
D018829:Adhesins, Bacterial / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018830:Adhesins, Escherichia coli; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000628:therapy; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D019496:Cancer Vaccines; D029968:Escherichia coli Proteins; D011993:Recombinant Fusion Proteins; C118376:antigen 43, E coli; D051496:Receptor, Fibroblast Growth Factor, Type 1