The silencing of indoleamine 2,3-dioxygenase 1 (IDO1) in dendritic cells by siRNA-loaded lipid nanoparticles enhances cell-based cancer immunotherapy

Scientific Reports
Rikito EndoHideyoshi Harashima

Abstract

Cell-based therapy using dendritic cells (DC) represents a potent cancer immunotherapy. However, activated DC express indoleamine 2,3-dioxygenase 1 (IDO1), a counter-regulatory and tolerogenic molecule, leading to the inhibition of T cell activation and the promotion of T cell differentiation into regulatory T cells. Silencing the IDO1 gene in DC by small interfering RNA (siRNA) represents a potent therapeutic strategy. We report on the successful and efficient introduction of a siRNA targeting IDO1 into mouse DCs by a means of a multifunctional envelope-type nanodevice (MEND) containing a YSK12-C4 (YSK12-MEND). The YSK12-C4 has both fusogenic and cationic properties. The YSK12-MEND induced an effective level of gene silencing of IDO1 at siRNA doses in the range of 1-20 nM, a concentration that commercially available transfection reagents are not able to silence. The YSK12-MEND mediated IDO1 silencing had no effect on the characteristic determinants of DC phenotype such as CD11c, CD80 and MHC class II. The silencing of IDO1 in DC by the YSK12-MEND significantly enhanced the antitumor effect against E.G7-OVA tumor. Moreover, a decrease in the numbers of regulatory T cells in the tumor was observed in mice that were treated with ...Continue Reading

References

Oct 2, 2004·Nature Reviews. Immunology·Andrew L Mellor, David H Munn
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Francesca FallarinoPaolo Puccetti
Dec 30, 2006·Cancer Immunology, Immunotherapy : CII·Marion WobserJuergen C Becker
Nov 27, 2007·Advanced Drug Delivery Reviews·Kentaro KogureHideyoshi Harashima
Jun 19, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Takashi NakamuraHideyoshi Harashima
Aug 7, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Young-Woock NohBong Hyun Chung
Oct 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wei ChenBruce R Blazar
Jan 28, 2010·Arthritis Research & Therapy·Xiufen ZhengWei-Ping Min
Aug 20, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joshua D MezrichChristopher A Bradfield
Aug 2, 2011·Biological & Pharmaceutical Bulletin·Shota WarashinaHideyoshi Harashima
Nov 10, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jessica Godin-EthierRéjean Lapointe
Jan 11, 2012·Journal of the National Cancer Institute·Marie L HuberPeter Iversen
Feb 14, 2012·Accounts of Chemical Research·T NakamuraH Harashima
Aug 9, 2012·International Journal of Cancer. Journal International Du Cancer·Xiufen ZhengWeiping Min
Jul 31, 2013·Immunity·Daniel S Chen, Ira Mellman
Apr 15, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hiroko MiyabeHideyoshi Harashima
Nov 27, 2015·Current Opinion in Immunology·David H Munn, Vincenzo Bronte
Jan 29, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Shota WarashinaHideyoshi Harashima
Feb 4, 2016·Trends in Immunology·David H Munn, Andrew L Mellor
Jul 5, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yusuke SatoHideyoshi Harashima
Nov 29, 2016·Scientific Reports·Takashi NakamuraHideyoshi Harashima
Dec 21, 2016·Cell Research·Atsushi Tanaka, Shimon Sakaguchi
Feb 27, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Naoya MiuraHideyoshi Harashima
Oct 25, 2017·Therapeutic Delivery·Takashi Nakamura, Hideyoshi Harashima
Dec 17, 2017·Cancer Research·George C PrendergastAlexander J Muller
Mar 31, 2018·Frontiers in Immunology·Maarten VerstevenEva Lion
May 12, 2018·Science·Ken Garber
Nov 2, 2018·Molecular Pharmaceutics·Hideyuki MasudaHideyoshi Harashima

❮ Previous
Next ❯

Citations

Sep 17, 2020·Pharmaceuticals·Shabirul Haque, Sarah R Vaiselbuh
Dec 29, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yusuke SatoHideyoshi Harashima
Feb 19, 2021·Drug Discovery Today·Vignesh Kamath
Mar 12, 2021·Frontiers in Immunology·Mahdi Abdoli ShadbadBehzad Baradaran
Mar 14, 2021·Life Sciences·Md Abdus SubhanVladimir P Torchilin
Jun 7, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shan ZhuJingtao Chen
Feb 11, 2021·Angewandte Chemie·Elisabeth HennesHerbert Waldmann
Sep 12, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yuma YamadaHideyoshi Harashima
Jun 22, 2021·Frontiers in Bioengineering and Biotechnology·Giulio GiustariniGiulia Adriani
Jul 5, 2021·International Journal of Pharmaceutics·Manon BergerGéraldine Piel
Jul 4, 2021·Journal for Immunotherapy of Cancer·Takashi NakamuraHideyoshi Harashima
Aug 29, 2021·Pharmaceutics·Giovanna C N B LôboSônia N Báo
Oct 1, 2021·International Journal of Pharmaceutics·Takashi NakamuraHideyoshi Harashima

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
chemical modification
flow cytometry
FACS
PCR

Software Mentioned

ZETASIZER
Kaluza
GeoMean

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.