title: 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: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors: Hai-Long
authors: HL
authors: Zhang
authors: Chuang
authors: C
authors: Yuan
authors: Dong-Mei
authors: DM
authors: Zhang
authors: Hua-Shan
authors: HS
authors: Shi
authors: Meng
authors: M
authors: Li
authors: Zi-Chao
authors: ZC
authors: Luo
authors: Yang
authors: Y
authors: Wan
authors: Lian
authors: L
authors: Lu
authors: Shun-Tao
authors: ST
authors: Luo
authors: Li
authors: L
authors: Yang
mesh_terms: D000534:Alum Compounds; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000276:immunology* / Q000633:toxicity; D019496:Cancer Vaccines / Q000276:immunology / Q000633:toxicity; D002352:Carrier Proteins / Q000276:immunology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification / Q000276:immunology; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification; D016896:Treatment Outcome; D018074:Vaccines, Conjugate / Q000276:immunology* / Q000633:toxicity
chemical_list: D000534:Alum Compounds; D001426:Bacterial Proteins; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D002352:Carrier Proteins; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011993:Recombinant Fusion Proteins; D018074:Vaccines, Conjugate; C028581:CRM197 (non-toxic variant of diphtheria toxin); D016222:Fibroblast Growth Factor 2; C041524:aluminum sulfate