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CpG ODN1826 作为一种有前途的黏蛋白 1-麦芽糖结合蛋白疫苗佐剂,可诱导树突状细胞成熟并增强抗肿瘤免疫。

CpG ODN1826 as a Promising Mucin1-Maltose-Binding Protein Vaccine Adjuvant Induced DC Maturation and Enhanced Antitumor Immunity.

机构信息

Department of Immunology, College of Basic Medical Science, Jilin University, Xinjiang Street 125, Changchun 130021, China.

出版信息

Int J Mol Sci. 2018 Mar 20;19(3):920. doi: 10.3390/ijms19030920.

Abstract

Mucin 1 (), 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 -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.

摘要

黏蛋白 1 (MUC1) 作为一种癌基因,是肿瘤免疫治疗的一个有吸引力的靶点。麦芽糖结合蛋白 (MBP) 是一种有效的内源性佐剂,可以增强蛋白质的免疫原性。因此,我们实验室构建了一种重组 MUC1 和 MBP 抗肿瘤疫苗 (M-M)。为了增强 M-M 的抗肿瘤免疫活性,本研究中使用 CpG 寡脱氧核苷酸 1826 (CpG 1826) 作为佐剂进行了检查。CpG 1826 与 M-M 的联合应用显著抑制了表达的 B16 细胞生长,并延长了荷瘤小鼠的存活时间。它诱导了 MUC1 特异性抗体和 Th1 免疫反应,以及体内细胞毒性 T 淋巴细胞 (CTL) 的细胞毒性。进一步的研究表明,它在体外促进树突状细胞 (DC) 的成熟和激活,并向 Th1 表型倾斜。因此,我们的研究表明 CpG 1826 是一种有效的佐剂,为进一步的 M-M 临床研究奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5535/5877781/0aec1c8b5fdd/ijms-19-00920-g001.jpg

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