Enhancement of dendritic cell-based vaccine potency by targeting antigen to endosomal/lysosomal compartments

Tae Heung Kang, Jin Hyup Lee, Hyun Cheol Bae, Kyung Hee Noh, Jin Hee Kim, Chung Kil Song, Byung Chul Shin, Chien Fu Hung, T. C. Wu, Jong Sup Park, Tae Woo Kim

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Dendritic cells (DCs) are the central players in cancer immunotherapy because of their distinct ability to prime immune responses. In previous work with DNA vaccines, we described an intracellular targeting approach that routed a nuclear/cytoplasmic antigen, human papillomavirus (HPV) type 16 E7, into the endosomal and lysosomal compartments. It does so by linking E7 with the sorting signal of lysosome-associated membrane protein 1 (Sig/LAMP-1) to enhance the presentation of E7 antigen to MHC class I-restricted CD8+ T cells, as well as to MHC class II-restricted CD4+ T cells. To date, the Sig/LAMP-1 targeting strategy has not been tested in the context of DC-based vaccines. This study was designed to determine whether targeting HPV-16 E7 to the endosomal/lysosomal compartment can enhance the potency of DC vaccines. In immunological studies, DC-Sig/E7/LAMP-1 dramatically increased in vitro activation and in vivo expansion of E7-specific CD4+ and CD8+ T cells, compared with DC-E7 and DC-No insert. More importantly, in both tumor prevention and tumor treatment assays, DC-Sig/E7/LAMP-1 generated greater anti-tumor immunity against TC-1 than DC-E7. Our results demonstrate that linkage of the antigen gene to an endosomal/lysosomal targeting signal may greatly enhance the potency of DC-based vaccines.

Original languageEnglish
Pages (from-to)126-134
Number of pages9
JournalImmunology Letters
Volume106
Issue number2
DOIs
Publication statusPublished - 2006 Aug 15

Keywords

  • Dendritic cell
  • Human papillomavirus (HPV)
  • Immunotherapy
  • Lysosome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Kang, T. H., Lee, J. H., Bae, H. C., Noh, K. H., Kim, J. H., Song, C. K., Shin, B. C., Hung, C. F., Wu, T. C., Park, J. S., & Kim, T. W. (2006). Enhancement of dendritic cell-based vaccine potency by targeting antigen to endosomal/lysosomal compartments. Immunology Letters, 106(2), 126-134. https://doi.org/10.1016/j.imlet.2006.05.004