Enhancement of DC vaccine potency by activating the PI3K/AKT pathway with a small interfering RNA targeting PTEN

Jin Hee Kim, Tae Heung Kang, Kyung Hee Noh, Seok Ho Kim, Young Ho Lee, Keon Woo Kim, Hyun Cheol Bae, Ye Hyeon Ahn, Eun Young Choi, Jin Seok Kim, Kyung Mi Lee, Tae Woo Kim

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Dendritic cell (DC)-based cancer vaccines have become important as an immunotherapeutics in generating anti-tumor immune responses. Due to a short lifespan of DCs, however, clinical application of current DC vaccines has been limited. Recently, activation of AKT/protein kinase B (PKB), a major effector of phosphatidylinositol 3-kinase (PI3K), has been reported as a critical factor in both activation and survival of DCs. We here improved the potency of a DC vaccine with a small interfering RNA (siRNA) targeting phosphatase and tensin homologue (PTEN), which is known to be a central negative regulator of the PI3K/AKT signal transduction cascade. Down-regulation of PTEN in DCs resulted in AKT dependent maturation, which in turn caused a significant up-regulation of surface expression in co-stimulatory molecules and the chemokine receptor, CCR7, leading to an increase of in vitro T cell activation activity and in vivo migration to a draining lymph node, respectively. Moreover, these PTEN siRNA-transfected DCs (DC/siPTEN) acquired an increased survival from the apoptotic death caused by GM-CSF deprivation or antigen-specific CD8+ T cell killing. Most importantly, DC/siPTEN generated more tumor antigen-specific CD8+ T cells and stronger anti-tumor effects in vaccinated mice than did control DCs (DC/siGFP). Thus, our data indicate that manipulation of the PI3K/AKT pathway via siRNA system could improve the efficacy of a DC-based tumor vaccine.

Original languageEnglish
Pages (from-to)47-54
Number of pages8
JournalImmunology Letters
Volume134
Issue number1
DOIs
Publication statusPublished - 2010 Nov 30

Bibliographical note

Funding Information:
This work was supported by a grant from the Innovative Research Institute for Cell Therapy , Republic of Korea ( A062260 ), a grant from the Basic Research Program of the Korea Science & Engineering Foundation (No. R1-2006-000-10565-0 ), a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare ( 070355 ), and a grant R11-2005-017-03003-0 from the Research Center for Women's Diseases of KOSEF . K.M. Lee was supported by a grant from KICOS ( K20704000007-09A0500-00710 ).

Keywords

  • AKT
  • Dendritic cell
  • Immunotherapy
  • PI3K
  • PTEN
  • SiRNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Enhancement of DC vaccine potency by activating the PI3K/AKT pathway with a small interfering RNA targeting PTEN'. Together they form a unique fingerprint.

Cite this