Synergistic antitumor effects of Escherichia coli maltose binding protein and Bacillus Calmette–Guerin in a mouse lung carcinoma model

Zhang, Qingyong; Ni, Wei; Zhao, Xin; Wang, Fengli; Gao, Zhuo; Tai, Guihua

doi:10.1016/j.imlet.2010.12.005

Cited by 19 publications

(15 citation statements)

References 22 publications

(23 reference statements)

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“…In addition to the immunostimulatory role, previous studies have also shown that MBP provides intrinsic maturation stimulus to DCs [7], induces Th1 cell activation, and increases the production of NO in mouse peritoneal macrophages [8,9]. In the present study, our results indicated that MBP had a direct effect on the activation and polarization of RAW264.7 macrophage cells into M1 lineage.…”

Section: Discussionsupporting

confidence: 73%

“…M1 macrophages, activated by LPS or IFN-γ, express a spectrum of proinflammatory cytokines, chemokines and effector molecules, such as IL-1β, IL-6, IL-12 and inducible nitric oxide synthase (iNOS); M2 macrophages, activated by IL-4, express a wide array of anti-inflammatory molecules, such as IL-10, TGF-β and arginase-1 (Arg-1). Our previous studies have shown that MBP enhances the production of inflammatory mediators and nitric oxide (NO) in mouse peritoneal macrophages and in macrophage cell lines [8,9,10]. Therefore, we hypothesize that, as a potent proinflammatory stimulus, MBP has the ability to polarize macrophages into M1 lineage.…”

Section: Introductionmentioning

confidence: 98%

“…MBP has been shown to induce dendritic cell (DC) activation and production of proinflammatory cytokines [7]. One of our previous studies has shown that MBP immunization induces activation of T helper type 1 (Th1) and natural killer (NK) cells in a mouse lung carcinoma model [8]. Furthermore, combined immunization with MBP and Bacillus Calmette-Guerin vaccine enhances the activation of macrophages in vivo [8].…”

Section: Introductionmentioning

confidence: 99%

“…One of our previous studies has shown that MBP immunization induces activation of T helper type 1 (Th1) and natural killer (NK) cells in a mouse lung carcinoma model [8]. Furthermore, combined immunization with MBP and Bacillus Calmette-Guerin vaccine enhances the activation of macrophages in vivo [8]. The immunoadjuvant effect of MBP has been further demonstrated in our follow-up study of mouse peritoneal macrophages stimulated with lipopolysaccharide (LPS), and the activity of MBP is likely to be mediated by toll-like receptor 2 (TLR2) and TLR4 signaling pathways [9].…”

Section: Introductionmentioning

confidence: 99%

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Escherichia coli Maltose-Binding Protein Induces M1 Polarity of RAW264.7 Macrophage Cells via a TLR2- and TLR4-Dependent Manner

Wang

Yuan

Liu

et al. 2015

IJMS

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Maltose-binding protein (MBP) is a critical player of the maltose/maltodextrin transport system in Escherichia coli. Our previous studies have revealed that MBP nonspecifically induces T helper type 1 (Th1) cell activation and activates peritoneal macrophages obtained from mouse. In the present study, we reported a direct stimulatory effect of MBP on RAW264.7 cells, a murine macrophage cell line. When stimulated with MBP, the production of nitric oxide (NO), IL-1β, IL-6 and IL-12p70, and the expressions of CD80, MHC class II and inducible nitric oxide synthase (iNOS) were all increased in RAW264.7 cells, indicating the activation and polarization of RAW264.7 cells into M1 macrophages induced by MBP. Further study showed that MBP stimulation upregulated the expression of TLR2 and TLR4 on RAW264.7 cells, which was accompanied by subsequent phosphorylation of IκB-α and p38 MAPK. Pretreatment with anti-TLR2 or anti-TLR4 antibodies largely inhibited the phosphorylation of IκB-α and p38 MAPK, and greatly reduced MBP-induced NO and IL-12p70 production, suggesting that the MBP-induced macrophage activation and polarization were mediated by TLR2 and TLR4 signaling pathways. The observed results were independent of lipopolysaccharide contamination. Our study provides a new insight into a mechanism by which MBP enhances immune responses and warrants the potential application of MBP as an immune adjuvant in immune therapies.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Escherichia coli Maltose-Binding Protein Induces M1 Polarity of RAW264.7 Macrophage Cells via a TLR2- and TLR4-Dependent Manner

Wang

Yuan

Liu

et al. 2015

IJMS

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“…MBP has been utilized as a chaperone in various experimental vaccines, with recombinant protein-MBP found to enhance immunogenicity (26,27). Previous studies by our group demonstrated that MBP promotes lymphocyte proliferation, directly activates T helper type 1 (Th1) and natural killer (NK) cells and enhances Bacillus Calmette-Guerin (BCG)-induced Th1 cell activation (28,29). Therefore, it is hypothesized that an MBP-fused MUC1 protein may enhance the immunogenicity of MUC1.…”

Section: Muc1 and Maltose-binding Protein Recombinant Fusion Protein mentioning

confidence: 99%

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

Fang

et al. 2014

Molecular Medicine Reports

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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.

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A review on development of MUC1-based cancer vaccine

Gao

Cen

Han

2020

Biomedicine & Pharmacotherapy

100

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Synergistic antitumor effects of Escherichia coli maltose binding protein and Bacillus Calmette–Guerin in a mouse lung carcinoma model

Cited by 19 publications

References 22 publications

Escherichia coli Maltose-Binding Protein Induces M1 Polarity of RAW264.7 Macrophage Cells via a TLR2- and TLR4-Dependent Manner

Escherichia coli Maltose-Binding Protein Induces M1 Polarity of RAW264.7 Macrophage Cells via a TLR2- and TLR4-Dependent Manner

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

A review on development of MUC1-based cancer vaccine

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