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

Cited 26 time in Web of Science Cited 28 time in Scopus
Authors
Kim, Jin Hee; Kang, Tae Heung; Noh, Kyung Hee; Kim, Seok-Ho; Kim, Keon Woo; Ahn, Ye-Hyeon; Kim, Jin-Seok; Kim, Tae Woo; Lee, Kyung-Mi; Choi, Eun Young; Bae, Hyun Cheol; Lee, Young-Ho
Issue Date
2010-11-30
Publisher
ELSEVIER SCIENCE BV
Citation
IMMUNOLOGY LETTERS; Vol.134 1; 47-54
Keywords
Dendritic cellsiRNAImmunotherapyAKTPTENPI3K
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 (C) 2010 Elsevier B V All rights reserved
ISSN
0165-2478
Language
English
URI
http://hdl.handle.net/10371/78203
DOI
https://doi.org/10.1016/j.imlet.2010.08.008
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Journal Papers (저널논문_의학과)
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