A novel combined conjugate vaccine: enhanced immunogenicity of bFGF with CRM197 as a carrier protein.

Abstract

Tumor growth is partly dependent on tumor-associated angiogenesis, which is regulated by angiogenic growth factors. As the first angiogenic growth factor to be identified, basic fibroblast growth factor (bFGF) plays a major role in angiogensis and tumor growth and has been an effective target for anti-tumor therapy. However, due to its low immunogenicity, injection with bFGF alone cannot stimulate the body to produce a strong immune response. In this study, we investigated the role of CF (containing bFGF and CRM197) assisted by CpG and alum in enhancing antigen-specific immune response and suppressing the growth of murine colon carcinoma. The results revealed that compared to bFGF, CF could not stimulate NIH-3T3 fibroblast proliferation even at a concentration of 10 µg/ml in vitro. In vivo, the CF-CpG-alum produced a stronger antigen-specific immune response and inhibited tumor growth. The anti-tumor activity was associated with generating antigen-specific antibody, suppressing angiogenesis, promoting the apoptosis of tumor cells and inducing the mixed Th1 and Th2 responses. This indicates that CRM197 may be an innovative intramolecular adjuvant and provides a rational preservation for mouse CT26 colon carcinoma.

• Authors: Hai-Long Zhang, Chuang Yuan, Dong-Mei Zhang, Hua-Shan Shi, Meng Li, Zi-Chao Luo, Yang Wan, Lian Lu, Shun-Tao Luo, Li Yang
• Journal: Molecular medicine reports (Mol Med Rep) 2011 Sep-Oct Vol. 4 Issue 5 Pg. 857-63 ISSN: 1791-3004 [Electronic] Greece
• PMID: 21720718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alum Compounds
• Bacterial Proteins
• CPG-oligonucleotide
• Cancer Vaccines
• Carrier Proteins
• Immunoglobulin G
• Oligodeoxyribonucleotides
• Platelet Endothelial Cell Adhesion Molecule-1
• Recombinant Fusion Proteins
• Vaccines, Conjugate
• CRM197 (non-toxic variant of diphtheria toxin)
• Fibroblast Growth Factor 2
• aluminum sulfate

Topics

• Alum Compounds
• Animals
• Apoptosis
• Bacterial Proteins (immunology, toxicity)
• Cancer Vaccines (immunology, toxicity)
• Carrier Proteins (immunology)
• Female
• Fibroblast Growth Factor 2 (immunology)
• Genetic Vectors (genetics)
• Humans
• Immunity (immunology)
• Immunoglobulin G (blood, classification, immunology)
• In Situ Nick-End Labeling
• Mice
• Mice, Inbred BALB C
• NIH 3T3 Cells
• Neoplasms (blood supply, immunology)
• Neovascularization, Pathologic (pathology)
• Oligodeoxyribonucleotides (immunology)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Recombinant Fusion Proteins (isolation & purification)
• Treatment Outcome
• Vaccines, Conjugate (immunology, toxicity)