Enhancement of DNA vaccine potency by antigen linkage to IFN-Iγ-inducible protein-10

Tae Heung Kang, Keon Woo Kim, Hyun Cheol Bae, Seung Yong Seong, Tae Woo Kim

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)702-714
Number of pages13
JournalInternational Journal of Cancer
Volume128
Issue number3
DOIs
Publication statusPublished - 2011 Feb 1

Keywords

  • CD4 Th1 T-cells
  • CD8 T-cells
  • DNA vaccines
  • HPV-16 E7
  • IP-10
  • chemokines

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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