Recombinant protein rMBP-NAP restricts tumor progression by triggering antitumor immunity in mouse metastatic lung cancer

Can J Physiol Pharmacol. 2018 Feb;96(2):113-119. doi: 10.1139/cjpp-2017-0186. Epub 2017 Sep 1.

Abstract

Recombinant Helicobacter pylori neutrophil-activating protein fused with maltose-binding protein (rMBP-NAP), a potential TLR2 ligand, was reported to possess immunomodulatory effects on in situ tumors in our previous study. In the present work, we attempt to elucidate the effect of rMBP-NAP at the local immune modulation in B16-F10-induced metastatic lung cancer. Our results demonstrated that growth of B16-F10 melanoma metastases in the lung was significantly arrested after rMBP-NAP treatment, along with marked reduction in metastatic lung nodules and significant increase in survival. The treatment induced both local and systemic immune responses, which were associated with higher influx of CD4+/CD8+ T cells and drove toward Th1-like and cytotoxic immune environment. Moreover, rMBP-NAP also showed significant anti-angiogenic activity by reducing vascularization in lung tumor sections. rMBP-NAP could induce antitumor immunity through activating Th1 cells and producing pro-inflammatory cytokines, which are responsible for the effective cytotoxic immune response against cancer progression. Our findings indicate that rMBP-NAP might be a novel antitumor therapeutic strategy.

Keywords: Toll-like receptor; antitumor immunotherapy; cancer du poumon métastatique; immunomodulateur; immunomodulator; immunothérapie antitumorale; metastatic lung cancer; rMBP-NAP; récepteur de type Toll.

MeSH terms

  • Animals
  • Bacterial Proteins / therapeutic use*
  • Cell Proliferation / drug effects
  • Disease Progression*
  • Immunity* / drug effects
  • Immunity, Cellular / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / secondary*
  • Maltose-Binding Proteins / therapeutic use*
  • Melanoma, Experimental / pathology
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / drug therapy
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / therapeutic use*
  • Spleen / pathology
  • Survival Analysis
  • Th1 Cells / drug effects
  • Tumor Microenvironment / drug effects
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Bacterial Proteins
  • Maltose-Binding Proteins
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • neutrophil-activating protein A, Helicobacter pylori