A Human In Vitro Whole Blood Assay to Predict the Systemic Cytokine Response to Therapeutic Oligonucleotides Including siRNA

PLoS ONE

Volumn 8, Issue 8, 2013, Pages

  Coch, Christoph ^a   Lück, Christian ^a   Schwickart, Anna ^a   Putschli, Bastian ^a   Renn, Marcel ^a   Höller, Tobias ^a   Barchet, Winfried ^a   Hartmann, Gunther ^a   Schlee, Martin ^a  

^a UNIVERSITY HOSPITAL BONN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; CPG OLIGODEOXYNUCLEOTIDE; HEPARIN; HIRUDIN; OLIGONUCLEOTIDE; RETINOIC ACID INDUCIBLE PROTEIN I; SMALL INTERFERING RNA; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 8; TOLL LIKE RECEPTOR 9;

ARTICLE; ASSAY; CELL ASSAY; CONTROLLED STUDY; CYTOKINE RELEASE; CYTOKINE RESPONSE; HUMAN; HUMAN CELL; IN VITRO STUDY; INTERMETHOD COMPARISON; PERIPHERAL BLOOD MONONUCLEAR CELL; PROTEIN INDUCTION; WHOLE BLOOD ASSAY;

EID: 84881101924     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0071057     Document Type: Article

References (38)

1. Vaishnaw AK, Gollob J, Gamba-Vitalo C, Hutabarat R, Sah D, et al. (2010) A status report on RNAi therapeutics. Silence 1: 14 doi:10.1186/1758-907X-1-14.
2. Krieg AM, (2006) Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drug Discov 5: 471-484 doi:10.1038/nrd2059.
3. Barchet W, Wimmenauer V, Schlee M, Hartmann G, (2008) Accessing the therapeutic potential of immunostimulatory nucleic acids. Curr Opin Immunol 20: 389-395 doi:10.1016/j.coi.2008.07.007.
4. Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, et al. (2005) Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 11: 263-270 doi:10.1038/nm1191.
5. Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, et al. (1995) CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374: 546-549 doi:10.1038/374546a0.
6. Hartmann G, Battiany J, Poeck H, Wagner M, Kerkmann M, et al. (2003) Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-alpha induction in plasmacytoid dendritic cells. Eur J Immunol 33: 1633-1641 doi:10.1002/eji.200323813.
7. Hornung V, Ellegast J, Kim S, Brzózka K, Jung A, et al. (2006) 5′-Triphosphate RNA is the ligand for RIG-I. Science 314: 994-997 doi:10.1126/science.1132505.
8. Schlee M, Roth A, Hornung V, Hagmann CA, Wimmenauer V, et al. (2009) Recognition of 5′ triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus. Immunity 31: 25-34 doi:10.1016/j.immuni.2009.05.008.
9. Gitlin L, Barchet W, Gilfillan S, Cella M, Beutler B, et al. (2006) Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc Natl Acad Sci USA 103: 8459-8464 doi:10.1073/pnas.0603082103.
10. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, et al. (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441: 101-105 doi:10.1038/nature04734.
11. Schlee M, Hornung V, Hartmann G, (2006) siRNA and isRNA: two edges of one sword. Mol Ther 14: 463-470 doi:10.1016/j.ymthe.2006.06.001.
12. Judge AD, Sood V, Shaw JR, Fang D, McClintock K, et al. (2005) Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol 23: 457-462 doi:10.1038/nbt1081.
13. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, et al. (2006) Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 355: 1018-1028 doi:10.1056/NEJMoa063842.
14. Ushiyama S, Yamada T, Murakami Y, Kumakura S-I, Inoue S-I, et al. (2008) Preclinical pharmacology profile of CS-706, a novel cyclooxygenase-2 selective inhibitor, with potent antinociceptive and anti-inflammatory effects. Eur J Pharmacol 578: 76-86 doi:10.1016/j.ejphar.2007.08.034.
15. Huntjens DRH, Danhof M, Pasqua Della OE, (2005) Pharmacokinetic-pharmacodynamic correlations and biomarkers in the development of COX-2 inhibitors. Rheumatology (Oxford) 44: 846-859 doi:10.1093/rheumatology/keh627.
16. Laufer S, Luik S, (2010) Different methods for testing potential cyclooxygenase-1 and cyclooxygenase-2 inhibitors. Methods Mol Biol 644: 91-116 doi:_10.1007/978-1-59745-364-6_8.
17. Müller-Steinhardt M, Wortmeier K, Fricke L, Ebel B, Härtel C, (2009) The pharmacodynamic effect of sirolimus: individual variation of cytokine mRNA expression profiles in human whole blood samples. Immunobiology 214: 17-26 doi:10.1016/j.imbio.2008.04.002.
18. May L, van Bodegom D, Kuningas M, Meij JJ, de Craen AJM, et al. (2009) Performance of the whole-blood stimulation assay for assessing innate immune activation under field conditions. Cytokine 45: 184-189 doi:10.1016/j.cyto.2008.12.010.
19. Rosas-Ballina M, Goldstein RS, Gallowitsch-Puerta M, Yang L, Valdés-Ferrer SI, et al. (2009) The selective alpha7 agonist GTS-21 attenuates cytokine production in human whole blood and human monocytes activated by ligands for TLR2, TLR3, TLR4, TLR9, and RAGE. Mol Med 15: 195-202 doi:10.2119/molmed.2009.00039.
20. Wang JE, Solberg R, Okkenhaug C, Jørgensen PF, Krohn CD, et al. (2000) Cytokine modulation in experimental endotoxemia: characterization of an ex vivo whole blood model. Eur Surg Res 32: 65-73.
21. Langezaal I, Coecke S, Hartung T, (2001) Whole blood cytokine response as a measure of immunotoxicity. Toxicol In Vitro 15: 313-318.
22. Thurm CW, Halsey JF, (2005) Measurement of cytokine production using whole blood. Curr Protoc Immunol Chapter 7Unit 7.18B. doi:10.1002/0471142735.im0718bs66.
23. IDA J, SHRESTHA N, DESAI S, PAHWA S, HANEKOM W, et al. (2006) A whole blood assay to assess peripheral blood dendritic cell function in response to Toll-like receptor stimulation. Journal of Immunological Methods 310: 86-99 doi:10.1016/j.jim.2005.12.008.
24. Wouters IM, Douwes J, Thorne PS, Heederik D, Doekes G, (2002) Inter- and intraindividual variation of endotoxin- and β(1→3)-glucan-induced cytokine responses in a whole blood assay. Toxicology and Industrial Health 18: 15-27 doi:10.1191/0748233702th126oa.
25. Ludwig RJ, (2009) Therapeutic use of heparin beyond anticoagulation. Curr Drug Discov Technol 6: 281-289.
26. Smorenburg SM, Van Noorden CJ, (2001) The complex effects of heparins on cancer progression and metastasis in experimental studies. Pharmacol Rev 53: 93-105.
27. Opal SM, Kessler CM, Roemisch J, Knaub S, (2002) Antithrombin, heparin, and heparan sulfate. Crit Care Med 30: S325-31.
28. Hamm S, Latz E, Hangel D, Müller T, Yu P, et al. (2010) Alternating 2′-O-ribose methylation is a universal approach for generating non-stimulatory siRNA by acting as TLR7 antagonist. Immunobiology 215: 559-569 doi:10.1016/j.imbio.2009.09.003.
29. Krieg AM, Efler SM, Wittpoth M, Adhami Al MJ, Davis HL, (2004) Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist. J Immunother 27: 460-471.
30. Vicari AP, Schmalbach T, Lekstrom-Himes J, Morris ML, Adhami Al MJ, et al. (2007) Safety, pharmacokinetics and immune effects in normal volunteers of CPG 10101 (ACTILON), an investigational synthetic toll-like receptor 9 agonist. Antivir Ther (Lond.) 12: 741-751.
31. Hamzah J, Altin JG, Herringson T, Parish CR, Hämmerling GJ, et al. (2009) Targeted liposomal delivery of TLR9 ligands activates spontaneous antitumor immunity in an autochthonous cancer model. J Immunol 183: 1091-1098 doi:10.4049/jimmunol.0900736.
32. Erikçi E, Gursel M, Gürsel I, (2011) Differential immune activation following encapsulation of immunostimulatory CpG oligodeoxynucleotide in nanoliposomes. Biomaterials 32: 1715-1723 doi:10.1016/j.biomaterials.2010.10.054.
33. Zwiorek K, Bourquin C, Battiany J, Winter G, Endres S, et al. (2008) Delivery by cationic gelatin nanoparticles strongly increases the immunostimulatory effects of CpG oligonucleotides. Pharm Res 25: 551-562 doi:10.1007/s11095-007-9410-5.
34. Ishii KJ, Coban C, Kato H, Takahashi K, Torii Y, et al. (2006) A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA. Nat Immunol 7: 40-48 doi:10.1038/ni1282.
35. Stetson DB, Medzhitov R, (2006) Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. Immunity 24: 93-103 doi:10.1016/j.immuni.2005.12.003.
36. Ablasser A, Bauernfeind F, Hartmann G, Latz E, Fitzgerald KA, et al. (2009) RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol 10: 1065-1072 doi:10.1038/ni.1779.
37. Lankveld DPK, Van Loveren H, Baken KA, Vandebriel RJ, (2010) In vitro testing for direct immunotoxicity: state of the art. Methods Mol Biol 598: 401-423 doi:_10.1007/978-1-60761-401-2_26.
38. Janke M, Poth J, Wimmenauer V, Giese T, Coch C, et al. (2009) Selective and direct activation of human neutrophils but not eosinophils by Toll-like receptor 8. J Allergy Clin Immunol 123: 1026-1033 doi:10.1016/j.jaci.2009.02.015.