Anti-metastatic effect of the TM4SF5-specific peptide vaccine and humanized monoclonal antibody on colon cancer in a mouse lung metastasis model
| Autor: | Younghee Lee, Guang Wu, Dongbum Kim, Yong Sung Kim, Su In Lee, Hyung-Joo Kwon, Sangkyu Park, Ji-Hee Ha, Byoung Kwon Park, Jung Nam Kim, Han-Bum Park, Te Ha Kim, Avishekh Gautam |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.drug_class Colorectal cancer Peptide Antibodies Monoclonal Humanized Humanized antibody Monoclonal antibody Peptides Cyclic Mice 03 medical and health sciences 0302 clinical medicine Cell Movement TM4SF5 Cell Line Tumor peptide vaccine Animals Humans Medicine anti- metastatic effect Cell Proliferation chemistry.chemical_classification biology business.industry Liver Neoplasms Membrane Proteins HCT116 Cells medicine.disease Xenograft Model Antitumor Assays Virology Gene Expression Regulation Neoplastic Treatment Outcome 030104 developmental biology colon cancer Oncology chemistry Immunization monoclonal antibody 030220 oncology & carcinogenesis Hepatocellular carcinoma Colonic Neoplasms Injections Intravenous Vaccines Subunit biology.protein Peptide vaccine Antibody business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.13005 |
| Popis: | // Guang Wu 1, * , Dongbum Kim 1, * , Byoung Kwon Park 1 , Sangkyu Park 2 , Ji-Hee Ha 3 , Te Ha Kim 4 , Avishekh Gautam 4 , Jung Nam Kim 4 , Su In Lee 4 , Han-Bum Park 2 , Yong-Sung Kim 3 , Hyung-Joo Kwon 1, 4 , Younghee Lee 2 1 Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea 2 Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea 3 Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea 4 Department 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 |
| Databáze: | OpenAIRE |
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