Fang Fang, Ma Jichun, Ni Weihua, Wang Fengli, Sun Xiaxia, Li Yingying, Li Qiongshu, Xie Fei, Wang Juan, Zhai Ruiping, Liu Zhonghui, Gao Sunjun, Tai Guixiang
Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2014 Aug;10(2):1056-64. doi: 10.3892/mmr.2014.2306. Epub 2014 Jun 10.
Human mucin 1 (MUC1) is a target for immunotherapy. The major problem associated with MUC1‑based cancer vaccines is the weakness of the immunogenicity of MUC1. The present study aimed to develop an efficient cancer vaccine through generating a recombinant fusion protein consisting of MUC1 and maltose‑binding protein (MBP) by inserting seven tandem repeats encoding the human MUC1 gene into the pMAL‑c2 expression vector. Bacillus Calmette‑Guerin (BCG) was used as an adjuvant. MUC1 was found to predominantly induce T helper type 2 (Th2) cell responses. MUC1/BCG and MUC1‑MBP were found to generate T helper (Th) type 1 and 2 responses, while MUC1‑MBP/BCG induced a Th1 immune profile and stimulated MUC1‑specific cytotoxic T lymphocyte killing activity. MUC1‑MBP, as well as MBP and BCG alone were found to induce natural killer (NK) cell activity, with MUC1‑MBP/BCG observed to synergistically induce NK cell activity. Furthermore, MUC1‑MBP/BCG significantly inhibited MUC1+ B16 cell growth in mice. These findings show that MBP augments the immunogenicity of MUC1 and that BCG enhances the efficacy of the MUC1‑MBP vaccine. Thus, MUC1‑MBP/BCG may have potential as a cancer vaccine for clinical application.
人黏蛋白1(MUC1)是免疫治疗的一个靶点。与基于MUC1的癌症疫苗相关的主要问题是MUC1免疫原性较弱。本研究旨在通过将编码人MUC1基因的七个串联重复序列插入pMAL-c2表达载体,构建由MUC1和麦芽糖结合蛋白(MBP)组成的重组融合蛋白,从而开发一种高效的癌症疫苗。卡介苗(BCG)用作佐剂。发现MUC1主要诱导2型辅助性T细胞(Th2)反应。发现MUC1/BCG和MUC1-MBP产生1型和2型辅助性T细胞(Th)反应,而MUC1-MBP/BCG诱导Th1免疫谱并刺激MUC1特异性细胞毒性T淋巴细胞杀伤活性。发现MUC1-MBP以及单独的MBP和BCG均可诱导自然杀伤(NK)细胞活性,观察到MUC1-MBP/BCG可协同诱导NK细胞活性。此外,MUC1-MBP/BCG可显著抑制小鼠体内MUC1+B16细胞的生长。这些发现表明,MBP增强了MUC1的免疫原性,BCG增强了MUC1-MBP疫苗的效力。因此,MUC1-MBP/BCG可能具有作为临床应用癌症疫苗的潜力。