Enhancement of DNA vaccine potency by antigen linkage to IFN-γ-inducible protein-10.
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.
Kang
Tae Heung
TH
Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Seoul, South Korea.
Kim
Keon Woo
KW
Bae
Hyun Cheol
HC
Seong
Seung-Yong
SY
Kim
Tae Woo
TW
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*
D016207:Cytokines; D017931:DNA Primers; D019444:Vaccines, DNA