MUC1 and maltose-binding protein recombinant fusion protein combined with Bacillus Calmette-Guerin induces MUC1-specific and nonspecific anti-tumor immunity in mice

作者: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*
来源:Molecular Medicine Reports, 2014, 10(2): 1056-1064.
DOI:10.3892/mmr.2014.2306

摘要

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.