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A peptide-CpG-DNA-liposome complex vaccine targeting TM4SF5 suppresses growth of pancreatic cancer in a mouse allograft model

Authors Park S, Kim D, Wu G, Jung H, Park JA, Kwon HJ, Lee Y

Received 5 September 2018

Accepted for publication 6 November 2018

Published 3 December 2018 Volume 2018:11 Pages 8655—8672

DOI https://doi.org/10.2147/OTT.S186606

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Narasimha Reddy Parine

Peer reviewer comments 2

Editor who approved publication: Dr Sanjay Singh


Sangkyu Park,1,2,* Dongbum Kim,3,* Guang Wu,3,4 Harry Jung,3 Jeong-A Park,1,2 Hyung-Joo Kwon,3,5 Younghee Lee1,2

1Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea; 2Biotechnology Research Institute, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea; 3Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea; 4School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; 5Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea

*These authors contributed equally to this work

Background: Patients with pancreatic cancer have a poor prognosis and are usually diagnosed at a late stage. Because TM4SF5 is known to be overexpressed in hepatocellular carcinoma, colon cancer, and pancreatic cancer, it is considered as one of the candidate molecular targets for an anticancer strategies.
Purpose: The purpose of this study was to evaluate possible utility of TM4SF5 to treat pancreatic cancer using a mouse allograft model.
Materials and methods: We analyzed expression of TM4SF5 in pancreatic cancer tissues using immunohistochemistry. We established a mouse pancreatic cancer cell line stably expressing TM4SF5 and identified the effect of TM4SF5 expression in vitro. We used the CpG-DNA-peptide-liposome complex as a peptide vaccine and investigated antitumor effects of the vaccine in a mouse model with TM4SF5 expressing pancreatic cells. To investigate the function of produced antibody, we evaluated effects of the anti-TM4SF5 monoclonal antibody in vitro in terms of cell growth and migration properties.
Results: Immunohistochemical analysis showed that 36.4% of pancreatic cancer tissue samples expressed TM4SF5. Expression of TM4SF5 induced increased cell proliferation and motility in vitro. Injection of the TM4SF5 peptide vaccine induced the production of anti-hTM4SF5 antibodies and reduced the growth of pancreatic tumors in mice established by subcutaneous injection of the TM4SF5-expressing mouse pancreatic cancer cell line. The treatment of TM4SF5-expressing cells with the anti-hTM4SF5 monoclonal antibody reduced cell growth, modulated the expression of the epithelial–mesenchymal transition markers Vimentin and E-cadherin, and decreased cell motility in vitro.
Conclusion: Our results showed that the TM4SF5 peptide vaccine had a protective effect against pancreatic tumors expressing TM4SF5, and this effect was mediated, at least in part, by the production and suppressive function of the anti-TM4SF5 antibodies. Therefore, we suggest that targeting TM4SF5 could be a novel strategy to prevent or treat pancreatic cancer.

Keywords: transmembrane 4 superfamily member 5 protein, pancreatic cancer, peptide vaccine, antibody, targeting

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