Enhanced induction of HIV-specific cytotoxic T lymphocytes by dendritic cell-targeted delivery of SOCS-1 siRNA.

Molecular Therapy : the Journal of the American Society of Gene Therapy
Sandesh SubramanyaPremlata Shankar

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in the activation of T cells. RNA interference (RNAi)-mediated silencing of negative immunoregulatory molecules expressed by DCs may provide a strategy to enhance the potency of DC-based vaccines and immunotherapy. Ablation of suppressor of cytokine signaling-1 (SOCS-1) in antigen-presenting cells has been shown to enhance cellular immune response in mice. Here, we used a previously reported DC-targeting approach to deliver small interfering RNA (siRNA) against SOCS-1 to human myeloid-derived DCs (MDDCs). SOCS1-silencing in MDDCs resulted in enhanced cytokine responses to lipopolysaccharide (LPS) and a strong mixed-lymphocyte reaction. Moreover, only DCs treated with SOCS-1 siRNA, and not controls, elicited strong primary in vitro responses to well-characterized HLA-A*0201-restricted Melan-A/MART-1 and human immunodeficiency virus (HIV) Gag epitopes in naive CD8(+) T cells from healthy donors. Finally, stimulation of CD8(+) T cells from HIV-seropositive subjects with SOCS1-silenced DCs resulted in an augmented polyfunctional cytotoxic T-lymphocyte (CTL) response, suggesting that SOCS-1 silencing can restore functionally compromised T cells in HI...Continue Reading

References

Aug 8, 1998·Trends in Cell Biology·I MellmanR M Steinman
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·R StarrW S Alexander
Jul 6, 2000·The Journal of Experimental Medicine·V AppayS L Rowland-Jones
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·J G ZhangN A Nicola
Feb 21, 2002·The Journal of Experimental Medicine·Alfred ZippeliusPedro Romero
Dec 13, 2002·Developmental and Comparative Immunology·Marie-Paule LefrancGérard Lefranc
Oct 27, 2004·Expert Opinion on Biological Therapy·Joseph G AltinChristopher R Parish
May 24, 2005·Nature Biotechnology·Erwei SongJudy Lieberman
Nov 8, 2005·Nature Biotechnology·Joao T Marques, Bryan R G Williams
Nov 17, 2005·The Journal of Experimental Medicine·David A PriceDaniel C Douek
Aug 22, 2006·Immunobiology·Paul J TackenCarl G Figdor
Sep 7, 2006·The Journal of Experimental Medicine·Constantinos PetrovasRichard A Koup
Jan 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·Leonia BozzaccoRalph M Steinman
Nov 1, 2007·European Journal of Immunology·Ralph M Steinman
Nov 11, 2008·Current Pharmaceutical Design·S M HensonA N Akbar
Dec 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Theron S JohnsonAlexander H Enk
Apr 4, 2009·Advanced Drug Delivery Reviews·N ManjunathPremlata Shankar
Sep 30, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sébastien WieckowskiNathalie Rufer

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Citations

Jul 14, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kathryn A WhiteheadDaniel G Anderson
Aug 21, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Soo Hyeon LeeJean-Christophe Leroux
Dec 12, 2012·Veterinary Immunology and Immunopathology·Mario Delgado-OrtegaFrançois Meurens
Dec 10, 2015·The Journal of Infectious Diseases·Bernard J C MacatangayCharles R Rinaldo
May 29, 2015·Genome Medicine·Maggie L BobbinJohn J Rossi
May 17, 2017·Advanced Drug Delivery Reviews·Ayelet David
Jul 15, 2017·AIDS Research and Therapy·Alexander KwartengGodwin Kwakye-Nuako
Jun 20, 2019·Frontiers in Immunology·Dagmar HildebrandKlaus Heeg
Jan 7, 2015·Bioconjugate Chemistry·Adi Golani-ArmonAyelet David

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