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

• Published in: Oncotarget 2016-11, Vol.7 (48), p.79170-79186
• Main Authors: Wu, Guang, Kim, Dongbum, Park, Byoung Kwon, Park, Sangkyu, Ha, Ji-Hee, Kim, Te Ha, Gautam, Avishekh, Kim, Jung Nam, Lee, Su In, Park, Han-Bum, Kim, Yong-Sung, Kwon, Hyung-Joo, Lee, Younghee
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - pharmacology; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Gene Expression Regulation, Neoplastic - drug effects; HCT116 Cells; Humans; Injections, Intravenous; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - secondary; Membrane Proteins - immunology; Membrane Proteins - metabolism; Mice; Peptides, Cyclic - administration & dosage; Peptides, Cyclic - pharmacology; Research Paper; Treatment Outcome; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - pharmacology; Xenograft Model Antitumor Assays
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.13005

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.