CpG ODN1826 as a Promising Mucin1-Maltose-Binding Protein Vaccine Adjuvant Induced DC Maturation and Enhanced Antitumor Immunity.
CpG ODN1826 as a Promising Mucin1-Maltose-Binding Protein Vaccine Adjuvant Induced DC Maturation and Enhanced Antitumor Immunity.
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DOI：
10.3390/ijms19030920
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发表时间：
2018-03-20
影响因子：
5.6
通讯作者：
Tai G
中科院分区：
文献类型：
--
作者：
Jie J;Zhang Y;Zhou H;Zhai X;Zhang N;Yuan H;Ni W;Tai G
粘蛋白1(MUC1)是一种癌基因，是肿瘤免疫治疗的重要靶点。麦芽糖结合蛋白(MBP)是一种增强蛋白质免疫原性的内置佐剂。为此，本实验室构建了重组MUC1和MBP抗肿瘤疫苗(M-M)。为了增强M-M的抗肿瘤免疫活性，本研究对Toll样受体-9激动剂CpG寡核苷酸1826(CpG 1826)作为佐剂进行了研究。M-M和CpG1826联合应用可显著抑制表达MUC1的B16细胞的生长，延长荷瘤小鼠的生存时间。在体内诱导MUC1特异性抗体和Th1免疫反应，以及细胞毒T淋巴细胞(CTL)细胞毒作用。进一步的研究表明，它能促进树突状细胞(DC)的成熟和激活，并在体外向Th1表型倾斜。因此，我们的研究表明CpG1826是一种有效的佐剂，为进一步的M-M临床研究奠定了基础。
Mucin 1 (MUC1), being an oncogene, is an attractive target in tumor immunotherapy. Maltose binding protein (MBP) is a potent built-in adjuvant to enhance protein immunogenicity. Thus, a recombinant MUC1 and MBP antitumor vaccine (M-M) was constructed in our laboratory. To enhance the antitumor immune activity of M-M, CpG oligodeoxynucleotides 1826 (CpG 1826), a toll-like receptor-9 agonist, was examined in this study as an adjuvant. The combination of M-M and CpG 1826 significantly inhibited MUC1-expressing B16 cell growth and prolonged the survival of tumor-bearing mice. It induced MUC1-specific antibodies and Th1 immune responses, as well as the Cytotoxic T Lymphocytes (CTL) cytotoxicity in vivo. Further studies showed that it promoted the maturation and activation of the dendritic cell (DC) and skewed towards Th1 phenotype in vitro. Thus, our study revealed that CpG 1826 is an efficient adjuvant, laying a foundation for further M-M clinical research.
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