Antitumor and immunomodulatory effects of recombinant fusion protein rMBP-NAP through TLR-2 dependent mechanism in tumor bearing mice

Int Immunopharmacol. 2015 Dec;29(2):876-883. doi: 10.1016/j.intimp.2015.08.027. Epub 2015 Sep 16.

Abstract

The pro-inflammatory and immunomodulatory properties of Helicobacter pylori neutrophil activating protein (Hp-NAP) not only make it to play an important role in disease pathogenesis but also make it to be a potential candidate for therapeutic applications, including vaccine and drug development. Our previous work demonstrated that the recombinant Hp-NAP fused with the maltose binding protein of Escherichia coli (rMBP-NAP) play an important role in regulating the differentiation of Th1 cells. In this study, we investigated the ability of rMBP-NAP to induce antitumor immunity using two murine models of hepatoma H22 and sarcoma S180. Subcutaneous administration of mice with rMBP-NAP resulted in an about 40%-50% decrease of tumor growth compared with that of the control mice. Splenocytes from the tumor-bearing mice treated with rMBP-NAP showed a significant accumulation of CD4(+) IFN-γ-secreting cells, which is a cytokine profile of Th1 cells. Furthermore, intravenous injection of T2.5, toll like receptor (TLR) 2 blocking antibody, significantly recede the antitumor effect of rMBP-NAP and the production of IFN-γ induced by rMBP-NAP. Our findings indicate that potentiality of rMBP-NAP to be a candidate for the development of immunomodulatory antitumoral drugs.

Keywords: Antitumor immunotherapy; TLR2; Th1 immune response; immunomudulatory drug; rMBP-NAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / pharmacology*
  • Bacterial Proteins / therapeutic use
  • Cancer Vaccines / pharmacology*
  • Cancer Vaccines / therapeutic use
  • Cell Differentiation / drug effects
  • Escherichia coli / metabolism
  • Female
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use
  • Immunotherapy / methods*
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / therapeutic use
  • Sarcoma 180 / drug therapy
  • Sarcoma 180 / immunology
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • Th1 Cells / drug effects
  • Toll-Like Receptor 2 / drug effects*

Substances

  • Bacterial Proteins
  • Cancer Vaccines
  • Immunologic Factors
  • Recombinant Fusion Proteins
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • neutrophil-activating protein A, Helicobacter pylori