Oncotarget

Research Papers:

Anti-metastatic effect of the TM4SF5-specific peptide vaccine and humanized monoclonal antibody on colon cancer in a mouse lung metastasis model

Guang Wu, Dongbum Kim, Byoung Kwon Park, Sangkyu Park, Ji-Hee Ha, Te Ha Kim, Avishekh Gautam, Jung Nam Kim, Su In Lee, Han-Bum Park, Yong-Sung Kim, Hyung-Joo Kwon and Younghee Lee _

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Oncotarget. 2016; 7:79170-79186. https://doi.org/10.18632/oncotarget.13005

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Abstract

Guang Wu1,*, Dongbum Kim1,*, Byoung Kwon Park1, Sangkyu Park2, Ji-Hee Ha3, Te Ha Kim4, Avishekh Gautam4, Jung Nam Kim4, Su In Lee4, Han-Bum Park2, Yong-Sung Kim3, Hyung-Joo Kwon1,4, Younghee Lee2

1Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea

2Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea

3Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea

4Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea

*These authors contributed equally to this work

Correspondence to:

Hyung-Joo Kwon, email: hjookwon@hallym.ac.kr

Younghee Lee, email: yhl4177@cbnu.ac.kr

Keywords: TM4SF5, peptide vaccine, monoclonal antibody, colon cancer, anti- metastatic effect

Received: August 19, 2016     Accepted: October 19, 2016     Published: November 01, 2016

ABSTRACT

Transmembrane 4 superfamily member 5 protein (TM4SF5) is a potential therapeutic target for hepatocellular carcinoma (HCC) and colon cancer. In a previous study, we demonstrated the prophylactic and therapeutic effects of a TM4SF5-specific peptide vaccine and monoclonal antibody in HCC and colon cancer in a mouse model. Here, we designed a cyclic peptide targeting TM4SF5. Cyclic peptide-specific antibodies were produced in mice after immunization with a complex of the peptide, CpG-DNA, and liposomes. Intravenous injection of the CT-26 mouse colon cancer cell line into mice induced tumors in the lung. Immunization with the peptide vaccine improved the survival rate and reduced the growth of lung tumors. We established a monoclonal antibody specific to the cyclic TM4SF5-based peptide and humanized the antibody sequence by complementarity determining region-grafting. The humanized antibody was reactive to the cyclic peptide and TM4SF5 protein. Treatment of CT-26 cells with the humanized antibody reduced cell motility in vitro. Furthermore, direct injection of the humanized anti-TM4SF5 antibody in vivo reduced growth of lung tumors in mouse metastasis model. Therefore, we conclude that the immunization with the cyclic peptide vaccine and injection of the TM4SF5-specifc humanized antibody have an anti-metastatic effect against colon cancer in mice. Importantly, the humanized antibody may serve as a starting platf


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