title: Prevention and therapy of hepatocellular carcinoma by vaccination with TM4SF5 epitope-CpG-DNA-liposome complex without carriers.
abstract: Although peptide vaccines have been actively studied in various animal models, their efficacy in treatment is limited. To improve the efficacy of peptide vaccines, we previously formulated an efficacious peptide vaccine without carriers using the natural phosphodiester bond CpG-DNA and a special liposome complex (Lipoplex(O)). Here, we show that immunization of mice with a complex consisting of peptide and Lipoplex(O) without carriers significantly induces peptide-specific IgG2a production in a CD4(+) cells- and Th1 differentiation-dependent manner. The transmembrane 4 superfamily member 5 protein (TM4SF5) has gained attention as a target for hepatocellular carcinoma (HCC) therapy because it induces uncontrolled growth of human HCC cells via the loss of contact inhibition. Monoclonal antibodies specific to an epitope of human TM4SF5 (hTM4SF5R2-3) can recognize native mouse TM4SF5 and induce functional effects on mouse cancer cells. Pre-immunization with a complex of the hTM4SF5R2-3 epitope and Lipoplex(O) had prophylactic effects against tumor formation by HCC cells implanted in an mouse tumor model. Furthermore, therapeutic effects were revealed regarding the growth of HCC when the vaccine was injected into mice after tumor formation. These results suggest that our improved peptide vaccine technology provides a novel prophylaxis measure as well as therapy for HCC patients with TM4SF5-positive tumors.
authors.affiliation: Department of Microbiology, College of Medicine, Hallym University, Gangwon-do, Republic of Korea.
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Kwon
authors.forename: Dongbum
authors.initials: D
authors.lastname: Kim
authors.forename: Byoung Kwon
authors.initials: BK
authors.lastname: Park
authors.forename: Sunhee
authors.initials: S
authors.lastname: Cho
authors.forename: Kwang Dong
authors.initials: KD
authors.lastname: Kim
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Kim
authors.forename: Cheung-Seog
authors.initials: CS
authors.lastname: Park
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Jae-Nam
authors.initials: JN
authors.lastname: Seo
authors.forename: Kyung-Chan
authors.initials: KC
authors.lastname: Choi
authors.forename: Doo-Sik
authors.initials: DS
authors.lastname: Kim
authors.forename: Younghee
authors.initials: Y
authors.lastname: Lee
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001973:Bromodeoxyuridine; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control* / Q000628:therapy*; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D018664:Interleukin-12 / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008081:Liposomes / Q000378:metabolism / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000628:therapy*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009838:Oligodeoxyribonucleotides; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000911:Antibodies, Monoclonal; C408982:CPG-oligonucleotide; D017931:DNA Primers; D007074:Immunoglobulin G; D008081:Liposomes; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; C570858:TM4SF5 protein, mouse; D013778:Tetrazolium Salts; D013844:Thiazoles; D018664:Interleukin-12; C022616:thiazolyl blue; D001973:Bromodeoxyuridine