Effects of Repeated Complement Activation Associated with Chronic Treatment of Cynomolgus Monkeys with 2′-O-Methoxyethyl Modified Antisense Oligonucleotide

Nucleic Acid Therapeutics

Volumn 26, Issue 4, 2016, Pages 236-249

  Shen, Lijiang ^a   Engelhardt, Jeffrey A ^a   Hung, Gene ^a   Yee, Jenna ^b   Kikkawa, Rie ^b   Matson, John ^a   Tayefeh, Bryan ^a   Machemer, Todd ^a   Giclas, Patricia C ^c   Henry, Scott P ^a  

^a ISIS PHARMACEUTICALS   (United States)

^b SNBL   (United States)

^c DEPARTMENT OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALTERNATIVE COMPLEMENT PATHWAY C3 C5 CONVERTASE; COMPLEMENT COMPONENT BB; COMPLEMENT COMPONENT C3A; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; ISIS 104838; UNCLASSIFIED DRUG; ANTISENSE OLIGONUCLEOTIDE; OLIGONUCLEOTIDE PHOSPHOROTHIOATE; TUMOR NECROSIS FACTOR;

ANIMAL TISSUE; ANTIGEN ANTIBODY COMPLEX; ARTICLE; COMPLEMENT ACTIVATION; CONTROLLED STUDY; DRUG BLOOD LEVEL; FEMALE; HEART; HISTOPATHOLOGY; IMMUNE COMPLEX DEPOSITION; IMMUNOGLOBULIN BLOOD LEVEL; IMMUNOGLOBULIN DEPOSITION; IMMUNOHISTOCHEMISTRY; KIDNEY; LIVER; MACACA FASCICULARIS; MALE; NONHUMAN; PRIORITY JOURNAL; VASCULARIZATION; VASCULITIS; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; GENETICS; HUMAN;

ANIMALS; COMPLEMENT ACTIVATION; DOSE-RESPONSE RELATIONSHIP, DRUG; HEART; HUMANS; KIDNEY; LIVER; MACACA FASCICULARIS; OLIGONUCLEOTIDES, ANTISENSE; PHOSPHOROTHIOATE OLIGONUCLEOTIDES; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84981316315     PISSN: 21593337     EISSN: 21593345     Source Type: Journal    
DOI: 10.1089/nat.2015.0584     Document Type: Article

References (37)

1. Crooke R, B Baker and M Wedel. (2007). Cardiovascular therapeutic applications. In: Antisense Drug Technology, Principles, Strategies and Applications. Crooke ST, ed. Taylor & Francis Group, Boca Raton, FL, pp 601-640.
2. Henry SP, PC Giclas, J Leeds, M Pangburn, C Auletta, AA Levin and DJ Kornbrust. (1997). Activation of the alternative pathway of complement by a phosphorothioate oligonucleotide: potential mechanism of action. J Pharmacol Exp Ther 281:810-816.
3. Henry SP, D Monteith, DJ Kornbrust and AA Levin. (1997). Effects of Intravenous infusion of phosphorothioate oligonucleotides on coagulation, complement activation and hemodynamics. Nucleosides Nucleotides 16:1673-1676.
4. Shen L, A Frazer-Abel, PR Reynolds, PC Giclas, A Chappell, MK Pangburn, H Younis and SP Henry. (2014). Mechanistic understanding for the greater sensitivity of monkeys to antisense oligonucleotide-mediated complement activation compared with humans. J Pharmacol Exp Ther 351:709-717.
5. Henry SP, MA Jagels, TE Hugli, S Manalili, RS Geary, PC Giclas and AA Levin. (2014). Mechanism of alternative complement pathway dysregulation by a phosphorothioate oligonucleotide in monkey and human serum. Nucleic Acid Ther 24:326-335.
6. Sewell LK, RS Geary, BF Baker, JM Glover, TGK Mant, RZ Yu, JA Tami and AF Dorr. (2002). Phase I trial of ISIS 104838, a 2′-methoxyethyl modified antisense oligonucleotide targeting tumor necrosis factor-alpha. J Pharmacol Exp Ther 303:1334-1343.
7. Glover JM, JM Leeds, TG Mant, D Amin, DL Kisner, JE Zuckerman, RS Geary, AA Levin and WR Shanahan Jr. (1997). Phase I safety and pharmacokinetic profile of an intercellular adhesion molecule-1 antisense oligodeoxynucleotide (ISIS 2302). J Pharmacol Exp Ther 282:1173-1180.
8. Nemunaitis J, JT Holmlund, M Kraynak, D Richards, J Bruce, N Ognoskie, TJ Kwoh, R Geary, A Dorr, D Von Hoff and SG Eckhardt. (1999). Phase I evaluation of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C-alpha, in patients with advanced cancer. J Clin Oncol 17:3586-3595.
9. Kastelein JJ, MK Wedel, BF Baker, J Su, JD Bradley, RZ Yu, E Chuang, MJ Graham and RM Crooke. (2006). Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation 114:1729-1735.
10. Chi KN, E Eisenhauer, L Fazli, EC Jones, SL Goldenberg, J Powers, D Tu and ME Gleave. (2005). A phase I pharmacokinetic and pharmacodynamic study of OGX-011, a 2′-methoxyethyl antisense oligonucleotide to clusterin, in patients with localized prostate cancer. J Natl Cancer Inst 97:1287-1296.
11. Harbeck RJ and PC Giclas. (1991). Complement levels by radialimmunodiffusion. In: Diagnostic Immunology Laboratory Manual. Raven Press, New York, pp 9-20.
12. Henry SP, G Beattie, G Yeh, A Chappel, P Giclas, A Mortari, MA Jagels, DJ Kornbrust and AA Levin. (2002). Complement activation is responsible for acute toxicities in rhesus monkeys treated with a phosphorothioate oligodeoxynucleotide. Int Immunopharmacol 2:1657-1666.
13. Galbraith WM, WC Hobson, PC Giclas, PJ Schechter and S Agrawal. (1994). Complement activation and hemodynamic changes following intravenous administration of phosphorothioate oligonucleotides in the monkey. Antisense Res Dev 4:201-206.
14. Ballanti E, C Perricone, E Greco, M Ballanti, G Di Muzio, MS Chimenti and R Perricone. (2013). Complement and autoimmunity. Immunol Res 56:477-491.
15. Boackle SA. (2003). Complement and autoimmunity. Biomed Pharmacother 57:269-273.
16. Reis ES, DA Falcao and L Isaac. (2006). Clinical aspects and molecular basis of primary deficiencies of complement component C3 and its regulatory proteins factor I and factor H. Scand J Immunol 63:155-168.
17. Skattum L, B Gullstrand, E Holmstrom, VA Oxelius and L Truedsson. (2008). Serum bactericidal activity against Neisseria meningitidis in patients with C3 nephritic factors is dependent on IgG allotypes. Clin Immunol 129: 123-131.
18. Strate M, H Olsen and B Teisner. (1987). Bactericidal capacity against Neisseria meningitidis of normal human serum and sera with functional deficiencies of the third and eight complement factor. Eur J Clin Invest 17:226-230.
19. Nash JT, PR Taylor, M Botto, PJ Norsworthy, KA Davies and MJ Walport. (2001). Immune complex processing in C1q-deficient mice. Clin Exp Immunol 123:196-202.
20. Schifferli JA and RP Taylor. (1989). Physiological and pathological aspects of circulating immune complexes. Kidney Int 35:993-1003.
21. Davies KA, JA Schifferli and MJ Walport. (1994). Complement deficiency and immune complex disease. Springer Semin Immunopathol 15:397-416.
22. Sanchez-Cuenca JM. (1994). Complement mediated solubilization: role of the complement in the clearance of circulating immune-complexes. Allergol Immunopathol (Madr) 22:197-203.
23. Miyaike J, Y Iwasaki, A Takahashi, H Shimomura, H Taniguchi, N Koide, K Matsuura, T Ogura, K Tobe and T Tsuji. (2002). Regulation of circulating immune complexes by complement receptor type 1 on erythrocytes in chronic viral liver diseases. Gut 51:591-596.
24. Kavai M. (2008). Immune complex clearance by complement receptor type 1 in SLE. Autoimmun Rev 8:160-164.
25. Waxman FJ, LA Hebert, JB Cornacoff, ME VanAman, WL Smead, EH Kraut, DJ Birmingham and JM Taguiam. (1984). Complement depletion accelerates the clearance of immune complexes from the circulation of primates. J Clin Invest 74:1329-1340.
26. Genel F, AG Sjoholm, L Skattum and L Truedsson. (2005). Complement factor I deficiency associated with recurrent infections, vasculitis and immune complex glomerulonephritis. Scand J Infect Dis 37:615-618.
27. Smiley JD and SE Moore Jr. (1989). Immune-complex vasculitis: role of complement and IgG-Fc receptor functions. Am J Med Sci 298:267-277.
28. Dofferhoff AS, HJ de Jong, VJ Bom, J van der Meer, PC Limburg, HG de Vries-Hospers, J Marrink, PO Mulder and J Weits. (1992). Complement activation and the production of inflammatory mediators during the treatment of severe sepsis in humans. Scand J Immunol 24: 197-204.
29. Fischer WH, MA Jagels and TE Hugli. (1999). Regulation of IL-6 synthesis in human peripheral blood mononuclear cells by C3a and C3a(desArg). J Immunol 162:453-459.
30. Frazier KS. (2014). Species-specific inflammatory responses as a primary component for the development of glomerular lesions in mice and monkeys following chronic administration of a second-generation antisense oligonucleotide. Toxicol Pathol 42:923-935.
31. Farman CA and DJ Kornbrust. (2003). Oligodeoxynucleotide studies in primates: antisense and immune stimulatory indications. Toxicol Pathol 31 (Suppl):119-122.
32. Henry SP, T-W Kim, K Kramer-Stickland, TA Zanardi, RA Fey and AA Levin. (2007). Toxicologic properties of 2′-Omethoxyethyl chimeric antisense inhibitors in animals and man. In: Antisense Drug Technology, Principles, Strategies and Applications. Crooke ST, ed. Taylor & Francis Group, Boca Raton, FL, pp 327-364.
33. Talbot DC, M Ranson, J Davies, M Lahn, S Callies, V Andre, S Kadam, M Burgess, C Slapak, et al. (2010). Tumor survivin is downregulated by the antisense oligonucleotide LY2181308: a proof-of-concept, first-in-human dose study. Clin Cancer Res 16:6150-6158.
34. TaniokaM,HNokihara,NYamamoto,YYamada,KYamada, Y Goto, T Fujimoto, R Sekiguchi, K Uenaka, S Callies and T Tamura. (2011). Phase I study of LY2181308, an antisense oligonucleotide against survivin, in patients with advanced solid tumors. Cancer Chemother Pharmacol 68:505-511.
35. Rudin CM, J Holmlund, GF Fleming, S Mani, WM Stadler, P Schumm, BP Monia, JF Johnston, R Geary, et al. (2001). Phase I Trial of ISIS 5132, an antisense oligonucleotide inhibitor of c-raf-1, administered by 24-hour weekly infusion to patients with advanced cancer. Clin Cancer Res 7:1214-1220.
36. Advani R, BL Lum, GA Fisher, J Halsey, RS Geary, JT Holmlund, TJ Kwoh, FA Dorr and BI Sikic. (2005). A phase I trial of aprinocarsen (ISIS 3521/LY900003), an antisense inhibitor of protein kinase C-alpha administered as a 24-hour weekly infusion schedule in patients with advanced cancer. Invest New Drugs 23: 467-477.
37. Yu RZ, JS Grundy, SP Henry, TW Kim, DA Norris, J Burkey, Y Wang, A Vick and RS Geary. (2015). Predictive dose-based estimation of systemic exposure multiples in mouse and monkey relative to human for antisense oligonucleotides with 2′-o-(2-methoxyethyl) modifications. Mol Ther Nucleic Acids 4:e218.