Innovative thrombolytic strategy using a heterodimer diabody against TAFI and PAI-1 in mouse models of thrombosis and stroke

Blood

Volumn 125, Issue 8, 2015, Pages 1325-1332

  Wyseure, Tine ^a   Rubio, Marina ^b   Denorme, Frederik ^c   De Lizarrondo, Sara Martinez ^b   Peeters, Miet ^a   Gils, Ann ^a   De Meyer, Simon F ^c   Vivien, Denis ^b   Declerck, Paul J ^a  

^a DEPARTMENT OF PHARMACEUTICAL AND PHARMACOLOGICAL SCIENCES   (Belgium)

^b INSERM   (France)

^c UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ALTEPLASE; DIABODY; FIBRINOLYTIC AGENT; HEMOGLOBIN; HETERODIMER; PLASMINOGEN ACTIVATOR INHIBITOR 1; THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR; THROMBOPLASTIN; UNCLASSIFIED DRUG; BISPECIFIC ANTIBODY; HISTONE ACETYLTRANSFERASE; PROTEASE NEXIN I; SERPINE2 PROTEIN, MOUSE; TATA BINDING PROTEIN ASSOCIATED FACTOR; TATA-BINDING PROTEIN ASSOCIATED FACTOR 250 KDA; TRANSCRIPTION FACTOR IID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY ENGINEERING; ARTICLE; BLOOD CLOT LYSIS; BRAIN DAMAGE; BRAIN INJURY; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; CONTROLLED STUDY; DRUG EFFICACY; DRUG HALF LIFE; FEMALE; FIBRIN DEPOSITION; FUNCTIONAL STATUS; MIDDLE CEREBRAL ARTERY OCCLUSION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; REPERFUSION INJURY; SINGLE DRUG DOSE; THROMBOSIS; VENOUS THROMBOEMBOLISM; WESTERN BLOTTING; ANIMAL; C57BL MOUSE; CHEMISTRY; DISEASE MODEL; EXPERIMENTAL THERAPY; IMMUNOLOGY; IMMUNOTHERAPY; MALE; METABOLISM; PATHOLOGY; PROCEDURES; PROTEIN MULTIMERIZATION; STROKE;

ANIMALS; ANTIBODIES, BISPECIFIC; DISEASE MODELS, ANIMAL; FEMALE; FIBRINOLYTIC AGENTS; HISTONE ACETYLTRANSFERASES; IMMUNOTHERAPY; MALE; MICE; MICE, INBRED C57BL; PROTEIN MULTIMERIZATION; SERPIN E2; STROKE; TATA-BINDING PROTEIN ASSOCIATED FACTORS; THERAPIES, INVESTIGATIONAL; TRANSCRIPTION FACTOR TFIID; VENOUS THROMBOEMBOLISM;

EID: 84923377827     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2014-07-588319     Document Type: Article

References (58)

1. Heiss WD, Grond M, Thiel A, et al. Tissue at risk of infarction rescued by early reperfusion: a positron emission tomography study in systemic recombinant tissue plasminogen activator thrombolysis of acute stroke. J Cereb Blood Flow Metab. 1998;18(12):1298-1307.
2. Eissa A, Krass I, Bajorek BV. Optimizing the management of acute ischaemic stroke: a review of the utilization of intravenous recombinant tissue plasminogen activator (tPA). J Clin Pharm Ther. 2012;37(6):620-629.
3. Dávalos A. Thrombolysis in acute ischemic stroke: successes, failures, and new hopes. Cerebrovasc Dis. 2005;20(Suppl 2):135-139.
4. Rijken DC, Lijnen HR. New insights into the molecular mechanisms of the fibrinolytic system. J Thromb Haemost. 2009;7(1):4-13.
5. Bajzar L, Manuel R, Nesheim ME. Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor. J Biol Chem. 1995;270(24): 14477-14484.
6. Huntington JA, Read RJ, Carrell RW. Structure of a serpin-protease complex shows inhibition by deformation. Nature. 2000;407(6806):923-926.
7. Meltzer ME, Lisman T, de Groot PG, et al. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood. 2010;116(1): 113-121.
8. Leebeek FW, Goor MP, Guimaraes AH, et al. High functional levels of thrombin-activatable fibrinolysis inhibitor are associated with an increased risk of first ischemic stroke. J Thromb Haemost. 2005;3(10):2211-2218.
9. Vaughan DE, Rouleau JL, Ridker PM, Arnold JM, Menapace FJ, Pfeffer MA; HEART Study Investigators. Effects of ramipril on plasma fibrinolytic balance in patients with acute anterior myocardial infarction. Circulation. 1997;96(2): 442-447.
10. Thögersen AM, Jansson JH, Boman K, et al. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation. 1998; 98(21):2241-2247.
11. Fernandez-Cadenas I, Alvarez-Sabin J, Ribo M, et al. Influence of thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 gene polymorphisms on tissue-type plasminogen activator-induced recanalization in ischemic stroke patients. J Thromb Haemost. 2007;5(9): 1862-1868.
12. Brouns R, Heylen E, Sheorajpanday R, et al. Carboxypeptidase U (TAFIa) decreases the efficacy of thrombolytic therapy in ischemic stroke patients. Clin Neurol Neurosurg. 2009;111(2): 165-170.
13. Wyseure T, Declerck PJ. Novel or expanding current targets in fibrinolysis. Drug Discov Today. 2014;19(9):1476-1482.
14. Izuhara Y, Yamaoka N, Kodama H, et al. A novel inhibitor of plasminogen activator inhibitor-1 provides antithrombotic benefits devoid of bleeding effect in nonhuman primates. J Cereb Blood Flow Metab. 2010;30(5):904-912.
15. Wang YX, da Cunha V, Vincelette J, et al. A novel inhibitor of activated thrombin activatable fibrinolysis inhibitor (TAFIa)-part II: enhancement of both exogenous and endogenous fibrinolysis in animal models of thrombosis. Thromb Haemost. 2007;97(1):54-61.
16. Mutch NJ, Thomas L, Moore NR, Lisiak KM, Booth NA. TAFIa, PAI-1 and alpha-antiplasmin: complementary roles in regulating lysis of thrombi and plasma clots. J Thromb Haemost. 2007;5(4): 812-817.
17. Vercauteren E, Emmerechts J, Peeters M, Hoylaerts MF, Declerck PJ, Gils A. Evaluation of the profibrinolytic properties of an anti-TAFI monoclonal antibody in a mouse thromboembolism model. Blood. 2011;117(17): 4615-4622.
18. Van De Craen B, Scroyen I, Abdelnabi R, et al. Characterization of a panel of monoclonal antibodies toward mouse PAI-1 that exert a significant profibrinolytic effect in vivo. Thromb Res. 2011;128(1):68-76.
19. Berry CN, Lunven C, Lechaire I, Girardot C, O'Connor SE. Antithrombotic activity of a monoclonal antibody inducing the substrate form of plasminogen activator inhibitor type 1 in rat models of venous and arterial thrombosis. Br J Pharmacol. 1998;125(1):29-34.
20. Semeraro F, Ammollo CT, Gils A, Declerck PJ, Colucci M. Monoclonal antibodies targeting the antifibrinolytic activity of activated thrombinactivatable fibrinolysis inhibitor but not the antiinflammatory activity on osteopontin and C5a. J Thromb Haemost. 2013;11(12):2137-2147.
21. Debrock S, Declerck PJ. Neutralization of plasminogen activator inhibitor-1 inhibitory properties: identification of two different mechanisms. Biochim Biophys Acta. 1997; 1337(2):257-266.
22. Wyseure T, Gils A, Declerck PJ. Evaluation of the profibrinolytic properties of a bispecific antibodybased inhibitor against human and mouse thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1. J Thromb Haemost. 2013;11(11):2069-2071.
23. Hendrickx ML, Zatloukalova M, Hassanzadeh-Ghassabeh G, Muyldermans S, Gils A, Declerck PJ. Identification of a novel, nanobody-induced, mechanism of TAFI inactivation and its in vivo application. J Thromb Haemost. 2014;12(2): 229-236.
24. Hendrickx ML, Zatloukalova M, Hassanzadeh-Ghassabeh G, Muyldermans S, Gils A, Declerck PJ. In vitro and in vivo characterisation of the profibrinolytic effect of an inhibitory anti-rat TAFI nanobody. Thromb Haemost. 2014;111(5): 824-832.
25. Kleinschnitz C, De Meyer SF, Schwarz T, et al. Deficiency of von Willebrand factor protects mice from ischemic stroke. Blood. 2009;113(15): 3600-3603.
26. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 1986;17(3):472-476.
27. Moran PM, Higgins LS, Cordell B, Moser PC. Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human beta-amyloid precursor protein. Proc Natl Acad Sci USA. 1995;92(12):5341-5345.
28. Orset C, Macrez R, Young AR, et al. Mouse model of in situ thromboembolic stroke and reperfusion. Stroke. 2007;38(10):2771-2778.
29. Le Behot A, Gauberti M, Martinez De Lizarrondo S, et al. GpIba-VWF blockade restores vessel patency by dissolving platelet aggregates formed under very high shear rate in mice. Blood. 2014; 123(21):3354-3363.
30. Gauberti M, Montagne A, Marcos-Contreras OA, Le Béhot A, Maubert E, Vivien D. Ultra-sensitive molecular MRI of vascular cell adhesion molecule-1 reveals a dynamic inflammatory penumbra after strokes. Stroke. 2013;44(7): 1988-1996.
31. Vercauteren E, Peeters M, Hoylaerts MF, et al. The hyperfibrinolytic state of mice with combined thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 gene deficiency is critically dependent on TAFI deficiency. J Thromb Haemost. 2012;10(12): 2555-2562.
32. Muto Y, Suzuki K, Sato E, Ishii H. Carboxypeptidase B inhibitors reduce tissue factor-induced renal microthrombi in rats. Eur J Pharmacol. 2003;461(2-3):181-189.
33. Van De Craen B, Scroyen I, Vranckx C, et al. Maximal PAI-1 inhibition in vivo requires neutralizing antibodies that recognize and inhibit glycosylated PAI-1. Thromb Res. 2012;129(4): e126-e133.
34. Kipriyanov SM, Moldenhauer G, Schuhmacher J, et al. Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics. J Mol Biol. 1999;293(1):41-56.
35. Chandler WL, Alessi MC, Aillaud MF, Henderson P, Vague P, Juhan-Vague I. Clearance of tissue plasminogen activator (TPA) and TPA/ plasminogen activator inhibitor type 1 (PAI-1) complex: relationship to elevated TPA antigen in patients with high PAI-1 activity levels. Circulation. 1997;96(3):761-768.
36. Hacke W, Donnan G, Fieschi C, et al; ATLANTIS Trials Investigators; ECASS Trials Investigators; NINDS rt-PA Study Group Investigators. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004; 363(9411):768-774.
37. Kraft P, Schwarz T, Meijers JC, Stoll G, Kleinschnitz C. Thrombin-activatable fibrinolysis inhibitor (TAFI) deficient mice are susceptible to intracerebral thrombosis and ischemic stroke. PLoS ONE. 2010;5(7):e11658.
38. Nagashima M, Yin ZF, Zhao L, et al. Thrombinactivatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life. J Clin Invest. 2002; 109(1):101-110.
39. Develter J, Booth NA, Declerck PJ, Gils A. Bispecific targeting of thrombin activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 by a heterodimer diabody. J Thromb Haemost. 2008;6(11):1884-1891.
40. Zhang ZG, Chopp M, Goussev A, et al. Cerebral microvascular obstruction by fibrin is associated with upregulation of PAI-1 acutely after onset of focal embolic ischemia in rats. J Neurosci. 1999; 19(24):10898-10907.
41. Heye N, Cervos-Navarro J. Microthromboemboli in acute infarcts: analysis of 40 autopsy cases. Stroke. 1996;27(3):431-434.
42. Okada Y, Copeland BR, Fitridge R, Koziol JA, del Zoppo GJ. Fibrin contributes to microvascular obstructions and parenchymal changes during early focal cerebral ischemia and reperfusion. Stroke. 1994;25(9):1847-1853; editorial comment 1853-1854.
43. del Zoppo GJ, Mabuchi T. Cerebral microvessel responses to focal ischemia. J Cereb Blood Flow Metab. 2003;23(8):879-894.
44. Santamaría A, Oliver A, Borrell M, et al. Risk of ischemic stroke associated with functional thrombin-activatable fibrinolysis inhibitor plasma levels. Stroke. 2003;34(10):2387-2391.
45. Rooth E, Wallen H, Antovic A, et al. Thrombin activatable fibrinolysis inhibitor and its relationship to fibrinolysis and inflammation during the acute and convalescent phase of ischemic stroke. Blood Coagul Fibrinolysis. 2007;18(4):365-370.
46. de Bruijne EL, Gils A, Guimarães AH, et al. The role of thrombin activatable fibrinolysis inhibitor in arterial thrombosis at a young age: the ATTAC study. J Thromb Haemost. 2009;7(6):919-927.
47. Kristensen B, Malm J, Nilsson TK, Hultdin J, Carlberg B, Olsson T. Increased fibrinogen levels and acquired hypofibrinolysis in young adults with ischemic stroke. Stroke. 1998;29(11):2261-2267.
48. Lindgren A, Lindoff C, Norrving B, Astedt B, Johansson BB. Tissue plasminogen activator and plasminogen activator inhibitor-1 in stroke patients. Stroke. 1996;27(6):1066-1071.
49. Catto AJ, Carter AM, Stickland M, Bamford JM, Davies JA, Grant PJ. Plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphism and levels in subjects with cerebrovascular disease. Thromb Haemost. 1997;77(4):730-734.
50. Margaglione M, Di Minno G, Grandone E, et al. Abnormally high circulation levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with a history of ischemic stroke. Arterioscler Thromb. 1994;14(11):1741-1745.
51. Wang YF, Tsirka SE, Strickland S, Stieg PE, Soriano SG, Lipton SA. Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPAdeficient mice. Nat Med. 1998;4(2):228-231.
52. Kim EY, Heo JH, Lee SK, et al. Prediction of thrombolytic efficacy in acute ischemic stroke using thin-section noncontrast CT. Neurology. 2006;67(10):1846-1848.
53. Vivien D, Gauberti M, Montagne A, Defer G, Touzé E. Impact of tissue plasminogen activator on the neurovascular unit: from clinical data to experimental evidence. J Cereb Blood Flow Metab. 2011;31(11):2119-2134.
54. Dirnagl U, Endres M. Found in translation: preclinical stroke research predicts human pathophysiology, clinical phenotypes, and therapeutic outcomes. Stroke. 2014;45(5): 1510-1518.
55. Durand A, Chauveau F, Cho TH, et al. Spontaneous reperfusion after in situ thromboembolic stroke in mice. PLoS ONE. 2012; 7(11):e50083.
56. Ribo M, Alvarez-Sabín J, Montaner J, et al. Temporal profile of recanalization after intravenous tissue plasminogen activator: selecting patients for rescue reperfusion techniques. Stroke. 2006;37(4):1000-1004.
57. Lapergue B, Dang BQ, Desilles JP, et al. Highdensity lipoprotein-based therapy reduces the hemorrhagic complications associated with tissue plasminogen activator treatment in experimental stroke. Stroke. 2013;44(3):699-707.
58. Suzuki Y, Nagai N, Collen D. Comparative effects of microplasmin and tissue-type plasminogen activator (tPA) on cerebral hemorrhage in a middle cerebral artery occlusion model in mice. J Thromb Haemost. 2004;2(9):1617-1621.