title: Combined stimulation of TLR9 and 4.1BB augments Trp2 peptide vaccine-mediated melanoma rejection by increasing Ag-specific CTL activity and infiltration into tumor sites.
abstract: Peptide vaccines are a clinically applicable therapy shown to be effective in tumor control. In this study, Trp2 peptides plus CpG-oligodeoxynucleotide treatment was found to induce Ag-specific IFN-γ and CD8+CTL responses, and antitumor activity against large established melanoma (tumor size, 7mm). A combination of anti-4.1BB antibodies with Trp2 peptides+CpG-oligodeoxynucleotide increased the antitumor cure rate from 0% to 75%. This effect was concomitant with greater induction of Ag-specific CD8+CTLs and their infiltration into the tumor sites, highlighting the importance of combined stimulation of TLR9 and 4.1BB for achieving tumor eradication. These findings may have implications for designing peptide-based therapeutic vaccines for cancer-patients.
authors.affiliation: Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea. jsin1964@hanmail.net
authors.forename: Jeong-Im
authors.initials: JI
authors.lastname: Sin
authors.forename: Ha
authors.initials: H
authors.lastname: Kim
authors.forename: Euri
authors.initials: E
authors.lastname: Ahn
authors.forename: Yong Hwan
authors.initials: YH
authors.lastname: Jeon
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Sang-Yeul
authors.initials: SY
authors.lastname: Lee
authors.forename: Byungsuk
authors.initials: B
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D000951:Antigens, Neoplasm; C408982:CPG-oligonucleotide; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D022223:Vaccines, Subunit; C500290:peptide SVYDFFVWL; D007371:Interferon-gamma