A novel combined conjugate vaccine: enhanced immunogenicity of bFGF with CRM197 as a carrier protein.
A novel combined conjugate vaccine: enhanced immunogenicity of bFGF with CRM197 as a carrier protein.
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DOI：
10.3892/mmr.2011.521
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发表时间：
2011-09
影响因子：
3.4
通讯作者：
Hai-long Zhang;Chuang Yuan;Dong-Mei Zhang;Hua-Shan Shi;Meng Li;Zi-chao Luo;Y. Wan;Lian Lu;S. Luo;Li Yang-
中科院分区：
文献类型：
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作者：
Hai-long Zhang;Chuang Yuan;Dong-Mei Zhang;Hua-Shan Shi;Meng Li;Zi-chao Luo;Y. Wan;Lian Lu;S. Luo;Li Yang-
肿瘤生长部分依赖于肿瘤相关血管生成，而肿瘤相关血管生成受血管生成生长因子调节。碱性成纤维细胞生长因子（bFGF）作为第一个被鉴定的血管生成生长因子，在血管生成和肿瘤生长中发挥着重要作用，已成为抗肿瘤治疗的有效靶点。但由于bFGF的免疫原性较低，单独注射bFGF并不能刺激机体产生强烈的免疫反应。在本研究中，我们研究了CpG和明矾辅助下的CF（含有bFGF和CRM197）在增强抗原特异性免疫反应和抑制小鼠结肠癌生长方面的作用。结果显示，与bFGF相比，CF即使在体外浓度为10μg/ml也不能刺激NIH-3T3成纤维细胞增殖。在体内，CF-CpG-明矾产生更强的抗原特异性免疫反应并抑制肿瘤生长。抗肿瘤活性与产生抗原特异性抗体、抑制血管生成、促进肿瘤细胞凋亡以及诱导Th1和Th2混合反应有关。这表明CRM197可能是一种创新的分子内佐剂，为小鼠CT26结肠癌提供合理的保存。
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.