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

• Published in: International immunopharmacology 2015-12, Vol.29 (2), p.876-883
• Main Authors: Wang, Ting, Liu, Xilong, Ji, Zhenyu, Men, Yingli, Du, Mingxuan, Ding, Cong, Wu, Yahong, Liu, Xin, Kang, Qiaozhen
• Format: Article
• Language: English
• Subjects: Animals; Antitumor immunotherapy; 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; immunomudulatory drug; 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; rMBP-NAP; Sarcoma 180 - drug therapy; Sarcoma 180 - immunology; Spleen - cytology; Spleen - drug effects; Spleen - immunology; Th1 Cells - drug effects; Th1 immune response; TLR2; Toll-Like Receptor 2 - drug effects
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2015.08.027

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. •rMBP-NAP can activate the systemic immune response, and enhance the activities of activated Th1 cells.•rMBP-NAP can elicit a significant antitumor effect by inducing Th1 immune response.•Antitumor and immunomodulatory activities of rMBP-NAP depend on a Toll like receptor 2-triggered pathway.