Vaccination with a recombinant chicken FGFR-1 bypasses immunological tolerance against self-FGFR-1 in mice

Abstract

The possibility that a recombinant protein vaccine based on xenogenic homologous FGFR-1 of chicken induces production of autoantibodies against self-FGFR-1 in BALB/c mice was examined by using ELISA, Western blot analysis and ELISPOT assay respectively. Autoantibodies against mouse FGFR-1 were identified by Western blot analysis and ELISA. Compared with the two control groups, the number of APBCs, which were detected by ELISPOT assay, was significantly increased in the spleens of mice immunized with cFR1 (P<0.05). IgG1 and IgG2b, which were detected by ELISA, were the major subclasses and were substantially increased in response to chicken FGFR-1 when compared with control group. The recombinant chicken FGFR-1 protein used as a vaccine can induce autoantibodies against self-FGFR-1 in mice and provide a basis for the active immunotherapy of tumor angiogenesis.

Keywords

fibroblast growth factor receptor-1 / tumor angiogenesis / protein vaccine / active immunotherapy

References

[1] PowersC. J., McleskeyS. W., WellsteinA.. Fibroblast growth factors, their receptors and signaling. Endocine-Related Cancer, 2000, 7: 165-197

[2] KlintP., Claesson-WelshL.. Signal transduction by fibroblast growth factor receptors. Front Biosci, 1999, 15: 165-177

[3] ChaudhuriM. M., MoscatelliD., BasilicoC.. Involvement of the conserved acidic amino acid domain of FGF receptor 1 in ligand-receptor interactions. J Cell Physiol, 1993, 157: 209-216

[4] ValeskyM., SpangA. J., GregoryW. F., et al.. Noninvasive dynamic fluorescence Imaging of human melanomas reveals that targeted Inhibition of bFGF or FGFR-1 in melanoma cells blocks tumor growth by apoptosis. Molecular Medicine, 2002, 8(2): 103-111

[5] PlumS. M., HoladayJ. W., RuizA., et al.. Administration of a liposomal FGF-2 peptide vaccine leads to abrogation of FGF-2-mediated angiogenesis and tumor development. Vaccine, 2000, 19(9–10): 1294-1303

[6] UdayakumarT. S., KleinR. D., MalinerM. S., et al.. Aberrant expression of fibroblast growth factor receptor-1 in prostate epithelial cells allows induction of promatrilysin expression by fibroblast growth factors. Int J Cancer, 2001, 91(2): 187-192

[7] SeonB. K., HoriA., SasadaR., et al.. Suppression of solid tumor growth by immunoneutralizing monoclonal antibody against human basic fibroblast growth factor. Cancer Res, 1991, 51: 6180-6184

[8] GregorP. D., WolchokJ. D., FerroneC. R., et al.. CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems. Vaccine, 2004, 22(13–14): 1700-1708

[9] RoopaS., JeddD. W.. Tumor antigens for cancer immunotherapy: therapeutic potential of xenogeneic DNA vaccines. J Transl Med, 2004, 2(1): 12-23

[10] GregorP. D., WolchokJ. D., TuragaV., et al.. Induction of autoantibodies to syngeneic prostate-specific membrane antigen by xenogeneic vaccination. Int J Cancer, 2005, 116(3): 415-421

[11] ZhengS. J., HuangF. Y., ZhengS. P., et al.. Construction and identification of recombinant plasmid encoding extracellular domain of FGFR1 in Chicken. J Univ Sci Technol Huazhong[Med] (Chinese), 2006, 35(4): 433-435

[12] CzerkinskyC. C., NilssonL. A., NygrenH., et al.. A solid-phase enzyme-linked immunospot(ELISPOT) assay for enumeration of specific antibody-secreting cells. J. Immunol. Methods, 1983, 65: 109-121

[13] FolkmanJ.. Angiogenesis-dependent diseases. Semin Oncol, 2001, 28(6): 536-542

[14] ChengW. F., HungC. F., ChaiC. Y., et al.. Tumor-specific immunity and antiangiogenesis generated by a DNA vaccine encoding calreticulin linked to a tumor antigen. J. Clin. Invest, 2001, 108: 669-678

[15] BarinagaM.. Angiogenesis research. Cancer drugs found to work in new way. Science, 2000, 288: 245-255

[16] KornbergT. B., KrasnowM. A.. The Drosophila genome sequence: implications for biology and medicine. Science, 2000, 287: 2218-2220