Modification of dendritic cells with interferon-γ -inducible protein-10 gene to enhance vaccine potency

Tae Heung Kang, Hyun Cheol Bae, Seok Ho Kim, Soo-Hong Seo, Sang Wook Son, Eun Young Choi, Seung Yong Seong, Tae Woo Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Dendritic cell (DC)-based vaccines have become a promising modality in cancer immunotherapy. However, their ability to initiate tumor antigen-specific T cell immunity is limited in various negative-feedback mechanisms. The rapid down-regulation of chemokines, such as the interferon inducible protein of 10 kDa (IP-10), which chemoattracts activated antigen-specific CD8+ T cells, would represent negative-feedback regulation. Therefore, we attempted to improve DC vaccine potency by introducing the IP-10 gene retrovirally aiming to replenish the chemoattractive activity of DCs. Methods: We introduced IP-10 gene into DC2.4 cells, referred to as DC-IP10, using a retroviral system. Nonsecretable mIP-10-expressing DCs (DC-mIP10) were also prepared to evaluate the effects of secretion in IP-10-mediated modulation of DC biology. Additionally, in vitro and in vivo activation of antigen-specific T lymphocytes and in vivo anti-tumor effects induced by DC-IP10 or DC-mIP10 were determined. Results: The modification of DC2.4 cells with the IP-10 gene resulted in the secretion of functionally chemoattractive IP-10 and, unexpectedly, a significant up-regulation of surface expression in co-stimulatory molecules, such as CD40 and CD80, compared to that of DCs with vector control (DC-no insert). DC-mIP10 also displayed the partially matured phenotypes but failed to recruit antigen-specific T cells in an in vitro cell culture system. Consistently, DC-IP10 generated more tumor antigen-specific CD8+ T cells and stronger anti-tumor effects in vaccinated mice than did control DCs and DC-mIP10. Conclusions: The results obtained provide the groundwork for a future clinical translation of the chemokine-based genetic modification of DCs to increase their vaccine potency.

Original languageEnglish
Pages (from-to)889-898
Number of pages10
JournalJournal of Gene Medicine
Volume11
Issue number10
DOIs
Publication statusPublished - 2009 Dec 28

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Keywords

  • Cancer vaccine
  • Chemokine
  • Dendritic cell
  • Immunotherapy
  • IP-10

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)
  • Drug Discovery

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