title: Enhancement of DNA vaccine potency by antigen linkage to IFN-γ-inducible protein-10.
abstract: DNA vaccines have emerged as an attractive approach to generate antigen-specific T-cell immune response. Nevertheless, the potency of DNA vaccines still needs to be improved for cancer immunotherapy. In this study, we explored whether functional linkage of a Th1-polarizing chemokine, IP-10, to a model tumor antigen, human papillomavirus type 16 (HPV-16) E7, enhanced DNA vaccine potency. IP-10 linkage changed the location of E7 from the nucleus to the endoplasmic reticulum and led to the secretion of functionally chemoattractive chimeric IP-10/E7 protein. In addition, this linkage drastically enhanced the endogenous processing of E7 antigen through MHC class I. More importantly, we found that C57BL/6 mice intradermally vaccinated with IP-10/E7 DNA exhibited a dramatic increase in the number of E7-specific CD4(+) Th1 T-cells and CD8(+) T-cells and, consequently, were strongly resistant over the long term to E7-expressing tumors compared to mice vaccinated with wild-type E7 DNA. Thus, because of the increase in tumor antigen-specific T-cell immune responses obtained through both enhanced antigen presentation and chemoattraction, vaccination with DNA encoding IP-10 linked to a tumor antigen holds great promise for treating tumors.
authors.affiliation: Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Seoul, South Korea.
authors.forename: Tae Heung
authors.initials: TH
authors.lastname: Kang
authors.forename: Keon Woo
authors.initials: KW
authors.lastname: Kim
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Bae
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Seong
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
mesh_terms: D000818:Animals; D019067:Antibody-Dependent Enhancement; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology; D005784:Gene Amplification; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000628:therapy; D016133:Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D019444:Vaccines, DNA