Anti-metastatic effect of the TM4SF5-specific peptide vaccine and humanized monoclonal antibody on colon cancer in a mouse lung metastasis model.
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.
Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Guang
G
Wu
Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Dongbum
D
Kim
Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Byoung Kwon
BK
Park
Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea.
Sangkyu
S
Park
Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea.
Ji-Hee
JH
Ha
Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Te Ha
TH
Kim
Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Avishekh
A
Gautam
Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Jung Nam
JN
Kim
Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Su In
SI
Lee
Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea.
Han-Bum
HB
Park
Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea.
Yong-Sung
YS
Kim
Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.|Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Hyung-Joo
HJ
Kwon
Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea.
Younghee
Y
Lee
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D061067:Antibodies, Monoclonal, Humanized; D008565:Membrane Proteins; D010456:Peptides, Cyclic; C111029:TM4SF5 protein, human; D022223:Vaccines, Subunit
TM4SF5; anti-  metastatic effect; colon cancer; monoclonal antibody; peptide vaccine