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Published in: Translational Stroke Research 5/2013

Open Access 01-10-2013 | Review Article

Therapeutic Antibodies in Stroke

Authors: Chye Yun Yu, Gandi Ng, Ping Liao

Published in: Translational Stroke Research | Issue 5/2013

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Abstract

Immunotherapy represents an active area of biomedical research to treat cancer, autoimmune diseases, and neurodegenerative disorders. In stroke, recanalization therapy is effective in reducing brain tissue damage after acute ischemic stroke. However, the narrow time window restricts its application for the majority of stroke patients. There is an urgent need to develop adjuvant therapies such as immunotherapy, stem cell replacement, and neuroprotective drugs. A number of molecules have been targeted for immunotherapy in stroke management, including myelin-associated proteins and their receptors, N-methyl-d-aspartic acid receptors, cytokines, and cell adhesion molecules. Both active vaccination and passive antibodies were tested in animal models of acute ischemic stroke. However, the mechanisms underlying the efficacy of immunotherapy are different for each target protein. Blocking myelin-associated proteins may enhance neuroplasticity, whereas blocking adhesion molecules may yield neuroprotection by suppressing the immune response after stroke. Although results from animal studies are encouraging, clinical trials using therapeutic antibodies failed to improve stroke outcome due to severe side effects. It remains a challenge to generate specific therapeutic antibodies with minimal side effects on other organs and systems.
Literature
1.
2.
3.
go back to reference Villoslada P, Moreno B, Melero I, Pablos JL, Martino G, Uccelli A, et al. Immunotherapy for neurological diseases. Clin Immunol. 2008;128:294–305.PubMedCrossRef Villoslada P, Moreno B, Melero I, Pablos JL, Martino G, Uccelli A, et al. Immunotherapy for neurological diseases. Clin Immunol. 2008;128:294–305.PubMedCrossRef
4.
go back to reference Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med. 2011;17:796–808.PubMedCrossRef Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med. 2011;17:796–808.PubMedCrossRef
5.
go back to reference Donnan GA, Davis SM. Stroke: expanded indications for stroke thrombolysis—what next? Nat Rev Neurol. 2012;8:482–3.PubMedCrossRef Donnan GA, Davis SM. Stroke: expanded indications for stroke thrombolysis—what next? Nat Rev Neurol. 2012;8:482–3.PubMedCrossRef
6.
7.
go back to reference Franklin RJ, Ffrench-Constant C, Edgar JM, Smith KJ. Neuroprotection and repair in multiple sclerosis. Nat Rev Neurol. 2012;8:624–34.PubMedCrossRef Franklin RJ, Ffrench-Constant C, Edgar JM, Smith KJ. Neuroprotection and repair in multiple sclerosis. Nat Rev Neurol. 2012;8:624–34.PubMedCrossRef
8.
go back to reference GrandPre T, Nakamura F, Vartanian T, Strittmatter SM. Identification of the Nogo inhibitor of axon regeneration as a reticulon protein. Nature. 2000;403:439–44.PubMedCrossRef GrandPre T, Nakamura F, Vartanian T, Strittmatter SM. Identification of the Nogo inhibitor of axon regeneration as a reticulon protein. Nature. 2000;403:439–44.PubMedCrossRef
9.
go back to reference Fournier AE, GrandPre T, Strittmatter SM. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature. 2001;409:341–6.PubMedCrossRef Fournier AE, GrandPre T, Strittmatter SM. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature. 2001;409:341–6.PubMedCrossRef
10.
go back to reference Caroni P, Schwab ME. Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron. 1988;1:85–96.PubMedCrossRef Caroni P, Schwab ME. Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron. 1988;1:85–96.PubMedCrossRef
11.
go back to reference Seymour AB, Andrews EM, Tsai SY, Markus TM, Bollnow MR, Brenneman MM, et al. Delayed treatment with monoclonal antibody IN-1 1 week after stroke results in recovery of function and corticorubral plasticity in adult rats. J Cereb Blood Flow Metab. 2005;25:1366–75.PubMedCrossRef Seymour AB, Andrews EM, Tsai SY, Markus TM, Bollnow MR, Brenneman MM, et al. Delayed treatment with monoclonal antibody IN-1 1 week after stroke results in recovery of function and corticorubral plasticity in adult rats. J Cereb Blood Flow Metab. 2005;25:1366–75.PubMedCrossRef
12.
go back to reference Tsai SY, Markus TM, Andrews EM, Cheatwood JL, Emerick AJ, Mir AK, et al. Intrathecal treatment with anti-Nogo-A antibody improves functional recovery in adult rats after stroke. Exp Brain Res. 2007;182:261–6.PubMedCrossRef Tsai SY, Markus TM, Andrews EM, Cheatwood JL, Emerick AJ, Mir AK, et al. Intrathecal treatment with anti-Nogo-A antibody improves functional recovery in adult rats after stroke. Exp Brain Res. 2007;182:261–6.PubMedCrossRef
13.
go back to reference Tsai SY, Papadopoulos CM, Schwab ME, Kartje GL. Delayed anti-Nogo-a therapy improves function after chronic stroke in adult rats. Stroke. 2011;42:186–90.PubMedCrossRef Tsai SY, Papadopoulos CM, Schwab ME, Kartje GL. Delayed anti-Nogo-a therapy improves function after chronic stroke in adult rats. Stroke. 2011;42:186–90.PubMedCrossRef
14.
go back to reference Papadopoulos CM, Tsai SY, Cheatwood JL, Bollnow MR, Kolb BE, Schwab ME, et al. Dendritic plasticity in the adult rat following middle cerebral artery occlusion and Nogo-a neutralization. Cereb Cortex. 2006;16:529–36.PubMedCrossRef Papadopoulos CM, Tsai SY, Cheatwood JL, Bollnow MR, Kolb BE, Schwab ME, et al. Dendritic plasticity in the adult rat following middle cerebral artery occlusion and Nogo-a neutralization. Cereb Cortex. 2006;16:529–36.PubMedCrossRef
15.
go back to reference Papadopoulos CM, Tsai SY, Alsbiei T, O’Brien TE, Schwab ME, Kartje GL. Functional recovery and neuroanatomical plasticity following middle cerebral artery occlusion and IN-1 antibody treatment in the adult rat. Ann Neurol. 2002;51:433–41.PubMedCrossRef Papadopoulos CM, Tsai SY, Alsbiei T, O’Brien TE, Schwab ME, Kartje GL. Functional recovery and neuroanatomical plasticity following middle cerebral artery occlusion and IN-1 antibody treatment in the adult rat. Ann Neurol. 2002;51:433–41.PubMedCrossRef
16.
go back to reference Wiessner C, Bareyre FM, Allegrini PR, Mir AK, Frentzel S, Zurini M, et al. Anti-Nogo-A antibody infusion 24 hours after experimental stroke improved behavioral outcome and corticospinal plasticity in normotensive and spontaneously hypertensive rats. J Cereb Blood Flow Metab. 2003;23:154–65.PubMedCrossRef Wiessner C, Bareyre FM, Allegrini PR, Mir AK, Frentzel S, Zurini M, et al. Anti-Nogo-A antibody infusion 24 hours after experimental stroke improved behavioral outcome and corticospinal plasticity in normotensive and spontaneously hypertensive rats. J Cereb Blood Flow Metab. 2003;23:154–65.PubMedCrossRef
17.
go back to reference Gillani RL, Tsai SY, Wallace DG, O’Brien TE, Arhebamen E, Tole M, et al. Cognitive recovery in the aged rat after stroke and anti-Nogo-A immunotherapy. Behav Brain Res. 2010;208:415–24.PubMedCrossRef Gillani RL, Tsai SY, Wallace DG, O’Brien TE, Arhebamen E, Tole M, et al. Cognitive recovery in the aged rat after stroke and anti-Nogo-A immunotherapy. Behav Brain Res. 2010;208:415–24.PubMedCrossRef
18.
go back to reference Ma J, Tian WM, Hou SP, Xu QY, Spector M, Cui FZ. An experimental test of stroke recovery by implanting a hyaluronic acid hydrogel carrying a Nogo receptor antibody in a rat model. Biomed Mater. 2007;2:233–40.PubMedCrossRef Ma J, Tian WM, Hou SP, Xu QY, Spector M, Cui FZ. An experimental test of stroke recovery by implanting a hyaluronic acid hydrogel carrying a Nogo receptor antibody in a rat model. Biomed Mater. 2007;2:233–40.PubMedCrossRef
19.
go back to reference Kilic E, ElAli A, Kilic U, Guo Z, Ugur M, Uslu U, et al. Role of Nogo-A in neuronal survival in the reperfused ischemic brain. J Cereb Blood Flow Metab. 2010;30:969–84.PubMedCrossRef Kilic E, ElAli A, Kilic U, Guo Z, Ugur M, Uslu U, et al. Role of Nogo-A in neuronal survival in the reperfused ischemic brain. J Cereb Blood Flow Metab. 2010;30:969–84.PubMedCrossRef
20.
go back to reference Irving EA, Vinson M, Rosin C, Roberts JC, Chapman DM, Facci L, et al. Identification of neuroprotective properties of anti-MAG antibody: a novel approach for the treatment of stroke? J Cereb Blood Flow Metab. 2005;25:98–107.PubMedCrossRef Irving EA, Vinson M, Rosin C, Roberts JC, Chapman DM, Facci L, et al. Identification of neuroprotective properties of anti-MAG antibody: a novel approach for the treatment of stroke? J Cereb Blood Flow Metab. 2005;25:98–107.PubMedCrossRef
21.
go back to reference Derfuss T, Meinl E. Identifying autoantigens in demyelinating diseases: valuable clues to diagnosis and treatment? Curr Opin Neurol. 2012;25:231–8.PubMedCrossRef Derfuss T, Meinl E. Identifying autoantigens in demyelinating diseases: valuable clues to diagnosis and treatment? Curr Opin Neurol. 2012;25:231–8.PubMedCrossRef
22.
go back to reference Frenkel D, Huang Z, Maron R, Koldzic DN, Hancock WW, Moskowitz MA, et al. Nasal vaccination with myelin oligodendrocyte glycoprotein reduces stroke size by inducing IL-10-producing CD4+ T cells. J Immunol. 2003;171:6549–55.PubMed Frenkel D, Huang Z, Maron R, Koldzic DN, Hancock WW, Moskowitz MA, et al. Nasal vaccination with myelin oligodendrocyte glycoprotein reduces stroke size by inducing IL-10-producing CD4+ T cells. J Immunol. 2003;171:6549–55.PubMed
23.
go back to reference The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581–7.CrossRef The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581–7.CrossRef
24.
go back to reference Nicole O, Docagne F, Ali C, Margaill I, Carmeliet P, MacKenzie ET, et al. The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling. Nat Med. 2001;7:59–64.PubMedCrossRef Nicole O, Docagne F, Ali C, Margaill I, Carmeliet P, MacKenzie ET, et al. The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling. Nat Med. 2001;7:59–64.PubMedCrossRef
25.
go back to reference During MJ, Symes CW, Lawlor PA, Lin J, Dunning J, Fitzsimons HL, et al. An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy. Science. 2000;287:1453–60.PubMedCrossRef During MJ, Symes CW, Lawlor PA, Lin J, Dunning J, Fitzsimons HL, et al. An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy. Science. 2000;287:1453–60.PubMedCrossRef
26.
go back to reference Benchenane K, Castel H, Boulouard M, Bluthe R, Fernandez-Monreal M, Roussel BD, et al. Anti-NR1 N-terminal-domain vaccination unmasks the crucial action of tPA on NMDA-receptor-mediated toxicity and spatial memory. J Cell Sci. 2007;120:578–85.PubMedCrossRef Benchenane K, Castel H, Boulouard M, Bluthe R, Fernandez-Monreal M, Roussel BD, et al. Anti-NR1 N-terminal-domain vaccination unmasks the crucial action of tPA on NMDA-receptor-mediated toxicity and spatial memory. J Cell Sci. 2007;120:578–85.PubMedCrossRef
27.
go back to reference Macrez R, Obiang P, Gauberti M, Roussel B, Baron A, Parcq J, et al. Antibodies preventing the interaction of tissue-type plasminogen activator with N-methyl-d-aspartate receptors reduce stroke damages and extend the therapeutic window of thrombolysis. Stroke. 2011;42:2315–22.PubMedCrossRef Macrez R, Obiang P, Gauberti M, Roussel B, Baron A, Parcq J, et al. Antibodies preventing the interaction of tissue-type plasminogen activator with N-methyl-d-aspartate receptors reduce stroke damages and extend the therapeutic window of thrombolysis. Stroke. 2011;42:2315–22.PubMedCrossRef
28.
go back to reference Macrez R, Bezin L, Le Mauff B, Ali C, Vivien D. Functional occurrence of the interaction of tissue plasminogen activator with the NR1 subunit of N-methyl-d-aspartate receptors during stroke. Stroke. 2010;41:2950–5.PubMedCrossRef Macrez R, Bezin L, Le Mauff B, Ali C, Vivien D. Functional occurrence of the interaction of tissue plasminogen activator with the NR1 subunit of N-methyl-d-aspartate receptors during stroke. Stroke. 2010;41:2950–5.PubMedCrossRef
29.
go back to reference Muir KW. Glutamate-based therapeutic approaches: clinical trials with NMDA antagonists. Curr Opin Pharmacol. 2006;6:53–60.PubMedCrossRef Muir KW. Glutamate-based therapeutic approaches: clinical trials with NMDA antagonists. Curr Opin Pharmacol. 2006;6:53–60.PubMedCrossRef
30.
go back to reference Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011;10:63–74.PubMedCrossRef Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011;10:63–74.PubMedCrossRef
31.
go back to reference Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci. 2010;30:5866–75.PubMedCrossRef Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci. 2010;30:5866–75.PubMedCrossRef
32.
go back to reference Matsuo Y, Kihara T, Ikeda M, Ninomiya M, Onodera H, Kogure K. Role of neutrophils in radical production during ischemia and reperfusion of the rat brain: effect of neutrophil depletion on extracellular ascorbyl radical formation. J Cereb Blood Flow Metab. 1995;15:941–7.PubMedCrossRef Matsuo Y, Kihara T, Ikeda M, Ninomiya M, Onodera H, Kogure K. Role of neutrophils in radical production during ischemia and reperfusion of the rat brain: effect of neutrophil depletion on extracellular ascorbyl radical formation. J Cereb Blood Flow Metab. 1995;15:941–7.PubMedCrossRef
33.
go back to reference Matsuo Y, Onodera H, Shiga Y, Nakamura M, Ninomiya M, Kihara T, et al. Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke. 1994;25:1469–75.PubMedCrossRef Matsuo Y, Onodera H, Shiga Y, Nakamura M, Ninomiya M, Kihara T, et al. Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke. 1994;25:1469–75.PubMedCrossRef
34.
go back to reference Zhang R, Chopp M, Zhang Z, Jiang N, Powers C. The expression of P- and E-selectins in three models of middle cerebral artery occlusion. Brain Res. 1998;785:207–14.PubMedCrossRef Zhang R, Chopp M, Zhang Z, Jiang N, Powers C. The expression of P- and E-selectins in three models of middle cerebral artery occlusion. Brain Res. 1998;785:207–14.PubMedCrossRef
35.
go back to reference Suzuki H, Abe K, Tojo SJ, Kitagawa H, Kimura K, Mizugaki M, et al. Reduction of ischemic brain injury by anti-P-selectin monoclonal antibody after permanent middle cerebral artery occlusion in rat. Neurol Res. 1999;21:269–76.PubMed Suzuki H, Abe K, Tojo SJ, Kitagawa H, Kimura K, Mizugaki M, et al. Reduction of ischemic brain injury by anti-P-selectin monoclonal antibody after permanent middle cerebral artery occlusion in rat. Neurol Res. 1999;21:269–76.PubMed
36.
go back to reference Suzuki H, Hayashi T, Tojo SJ, Kitagawa H, Kimura K, Mizugaki M, et al. Anti-P-selectin antibody attenuates rat brain ischemic injury. Neurosci Lett. 1999;265:163–6.PubMedCrossRef Suzuki H, Hayashi T, Tojo SJ, Kitagawa H, Kimura K, Mizugaki M, et al. Anti-P-selectin antibody attenuates rat brain ischemic injury. Neurosci Lett. 1999;265:163–6.PubMedCrossRef
37.
go back to reference Huang J, Choudhri TF, Winfree CJ, McTaggart RA, Kiss S, Mocco J, et al. Postischemic cerebrovascular E-selectin expression mediates tissue injury in murine stroke. Stroke. 2000;31:3047–53.PubMedCrossRef Huang J, Choudhri TF, Winfree CJ, McTaggart RA, Kiss S, Mocco J, et al. Postischemic cerebrovascular E-selectin expression mediates tissue injury in murine stroke. Stroke. 2000;31:3047–53.PubMedCrossRef
38.
go back to reference Ishibashi S, Maric D, Mou Y, Ohtani R, Ruetzler C, Hallenbeck JM. Mucosal tolerance to E-selectin promotes the survival of newly generated neuroblasts via regulatory T-cell induction after stroke in spontaneously hypertensive rats. J Cereb Blood Flow Metab. 2009;29:606–20.PubMedCrossRef Ishibashi S, Maric D, Mou Y, Ohtani R, Ruetzler C, Hallenbeck JM. Mucosal tolerance to E-selectin promotes the survival of newly generated neuroblasts via regulatory T-cell induction after stroke in spontaneously hypertensive rats. J Cereb Blood Flow Metab. 2009;29:606–20.PubMedCrossRef
39.
go back to reference Takeda H, Spatz M, Ruetzler C, McCarron R, Becker K, Hallenbeck J. Induction of mucosal tolerance to E-selectin prevents ischemic and hemorrhagic stroke in spontaneously hypertensive genetically stroke-prone rats. Stroke. 2002;33:2156–63.PubMedCrossRef Takeda H, Spatz M, Ruetzler C, McCarron R, Becker K, Hallenbeck J. Induction of mucosal tolerance to E-selectin prevents ischemic and hemorrhagic stroke in spontaneously hypertensive genetically stroke-prone rats. Stroke. 2002;33:2156–63.PubMedCrossRef
40.
go back to reference Yenari MA, Sun GH, Kunis DM, Onley D, Vexler V. L-selectin inhibition does not reduce injury in a rabbit model of transient focal cerebral ischemia. Neurol Res. 2001;23:72–8.PubMedCrossRef Yenari MA, Sun GH, Kunis DM, Onley D, Vexler V. L-selectin inhibition does not reduce injury in a rabbit model of transient focal cerebral ischemia. Neurol Res. 2001;23:72–8.PubMedCrossRef
41.
go back to reference Bednar MM, Gross CE, Russell SR, Fuller SP, Ellenberger CL, Schindler E, et al. Humanized anti-L-selectin monoclonal antibody DREG200 therapy in acute thromboembolic stroke. Neurol Res. 1998;20:403–8.PubMed Bednar MM, Gross CE, Russell SR, Fuller SP, Ellenberger CL, Schindler E, et al. Humanized anti-L-selectin monoclonal antibody DREG200 therapy in acute thromboembolic stroke. Neurol Res. 1998;20:403–8.PubMed
42.
go back to reference Rieckmann P, Nunke K, Burchhardt M, Albrecht M, Wiltfang J, Ulrich M, et al. Soluble intercellular adhesion molecule-1 in cerebrospinal fluid: an indicator for the inflammatory impairment of the blood–cerebrospinal fluid barrier. J Neuroimmunol. 1993;47:133–40.PubMedCrossRef Rieckmann P, Nunke K, Burchhardt M, Albrecht M, Wiltfang J, Ulrich M, et al. Soluble intercellular adhesion molecule-1 in cerebrospinal fluid: an indicator for the inflammatory impairment of the blood–cerebrospinal fluid barrier. J Neuroimmunol. 1993;47:133–40.PubMedCrossRef
43.
go back to reference Smith CW, Marlin SD, Rothlein R, Toman C, Anderson DC. Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J Clin Invest. 1989;83:2008–17.PubMedCrossRef Smith CW, Marlin SD, Rothlein R, Toman C, Anderson DC. Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J Clin Invest. 1989;83:2008–17.PubMedCrossRef
44.
go back to reference Frijns CJ, Kappelle LJ. Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke. 2002;33:2115–22.PubMedCrossRef Frijns CJ, Kappelle LJ. Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke. 2002;33:2115–22.PubMedCrossRef
45.
go back to reference Bowes MP, Zivin JA, Rothlein R. Monoclonal antibody to the ICAM-1 adhesion site reduces neurological damage in a rabbit cerebral embolism stroke model. Exp Neurol. 1993;119:215–9.PubMedCrossRef Bowes MP, Zivin JA, Rothlein R. Monoclonal antibody to the ICAM-1 adhesion site reduces neurological damage in a rabbit cerebral embolism stroke model. Exp Neurol. 1993;119:215–9.PubMedCrossRef
46.
go back to reference Chopp M, Li Y, Jiang N, Zhang RL, Prostak J. Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain. J Cereb Blood Flow Metab. 1996;16:578–84.PubMedCrossRef Chopp M, Li Y, Jiang N, Zhang RL, Prostak J. Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain. J Cereb Blood Flow Metab. 1996;16:578–84.PubMedCrossRef
47.
go back to reference Zhang RL, Chopp M, Li Y, Zaloga C, Jiang N, Jones ML, et al. Anti-ICAM-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat. Neurology. 1994;44:1747–51.PubMedCrossRef Zhang RL, Chopp M, Li Y, Zaloga C, Jiang N, Jones ML, et al. Anti-ICAM-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat. Neurology. 1994;44:1747–51.PubMedCrossRef
48.
go back to reference Bowes MP, Rothlein R, Fagan SC, Zivin JA. Monoclonal antibodies preventing leukocyte activation reduce experimental neurologic injury and enhance efficacy of thrombolytic therapy. Neurology. 1995;45:815–9.PubMedCrossRef Bowes MP, Rothlein R, Fagan SC, Zivin JA. Monoclonal antibodies preventing leukocyte activation reduce experimental neurologic injury and enhance efficacy of thrombolytic therapy. Neurology. 1995;45:815–9.PubMedCrossRef
49.
go back to reference Zhang RL, Chopp M, Jiang N, Tang WX, Prostak J, Manning AM, et al. Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat. Stroke. 1995;26:1438–42.PubMedCrossRef Zhang RL, Chopp M, Jiang N, Tang WX, Prostak J, Manning AM, et al. Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat. Stroke. 1995;26:1438–42.PubMedCrossRef
50.
go back to reference Enlimomab Acute Stroke Trial Investigators. Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology. 2001;57:1428–34.CrossRef Enlimomab Acute Stroke Trial Investigators. Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology. 2001;57:1428–34.CrossRef
51.
go back to reference Jaeschke H, Farhood A, Bautista AP, Spolarics Z, Spitzer JJ, Smith CW. Functional inactivation of neutrophils with a Mac-1 (CD11b/CD18) monoclonal antibody protects against ischemia–reperfusion injury in rat liver. Hepatology. 1993;17:915–23.PubMedCrossRef Jaeschke H, Farhood A, Bautista AP, Spolarics Z, Spitzer JJ, Smith CW. Functional inactivation of neutrophils with a Mac-1 (CD11b/CD18) monoclonal antibody protects against ischemia–reperfusion injury in rat liver. Hepatology. 1993;17:915–23.PubMedCrossRef
52.
go back to reference Simpson PJ, Todd 3rd RF, Fantone JC, Mickelson JK, Griffin JD, Lucchesi BR. Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. J Clin Invest. 1988;81:624–9.PubMedCrossRef Simpson PJ, Todd 3rd RF, Fantone JC, Mickelson JK, Griffin JD, Lucchesi BR. Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. J Clin Invest. 1988;81:624–9.PubMedCrossRef
53.
go back to reference Simpson PJ, Todd 3rd RF, Mickelson JK, Fantone JC, Gallagher KP, Lee KA, et al. Sustained limitation of myocardial reperfusion injury by a monoclonal antibody that alters leukocyte function. Circulation. 1990;81:226–37.PubMedCrossRef Simpson PJ, Todd 3rd RF, Mickelson JK, Fantone JC, Gallagher KP, Lee KA, et al. Sustained limitation of myocardial reperfusion injury by a monoclonal antibody that alters leukocyte function. Circulation. 1990;81:226–37.PubMedCrossRef
54.
go back to reference Chen H, Chopp M, Zhang RL, Bodzin G, Chen Q, Rusche JR, et al. Anti-CD11b monoclonal antibody reduces ischemic cell damage after transient focal cerebral ischemia in rat. Ann Neurol. 1994;35:458–63.PubMedCrossRef Chen H, Chopp M, Zhang RL, Bodzin G, Chen Q, Rusche JR, et al. Anti-CD11b monoclonal antibody reduces ischemic cell damage after transient focal cerebral ischemia in rat. Ann Neurol. 1994;35:458–63.PubMedCrossRef
55.
go back to reference Chopp M, Zhang RL, Chen H, Li Y, Jiang N, Rusche JR. Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats. Stroke. 1994;25:869–75.PubMedCrossRef Chopp M, Zhang RL, Chen H, Li Y, Jiang N, Rusche JR. Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats. Stroke. 1994;25:869–75.PubMedCrossRef
56.
go back to reference Bednar MM, Wright SD, Raymond-Russell SJ, Kohut JJ, Gross CE. IB4, a monoclonal antibody against the CD18 leukocyte adhesion protein, reduces intracranial pressure following thromboembolic stroke in the rabbit. Neurol Res. 1996;18:171–5.PubMed Bednar MM, Wright SD, Raymond-Russell SJ, Kohut JJ, Gross CE. IB4, a monoclonal antibody against the CD18 leukocyte adhesion protein, reduces intracranial pressure following thromboembolic stroke in the rabbit. Neurol Res. 1996;18:171–5.PubMed
57.
go back to reference Colditz I, Zwahlen R, Dewald B, Baggiolini M. In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human monocytes. Am J Pathol. 1989;134:755–60.PubMed Colditz I, Zwahlen R, Dewald B, Baggiolini M. In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human monocytes. Am J Pathol. 1989;134:755–60.PubMed
58.
go back to reference Huber AR, Kunkel SL, Todd 3rd RF, Weiss SJ. Regulation of transendothelial neutrophil migration by endogenous interleukin-8. Science. 1991;254:99–102.PubMedCrossRef Huber AR, Kunkel SL, Todd 3rd RF, Weiss SJ. Regulation of transendothelial neutrophil migration by endogenous interleukin-8. Science. 1991;254:99–102.PubMedCrossRef
59.
go back to reference Al-Bahrani A, Taha S, Shaath H, Bakhiet M. TNF-alpha and IL-8 in acute stroke and the modulation of these cytokines by antiplatelet agents. Curr Neurovasc Res. 2007;4:31–7.PubMedCrossRef Al-Bahrani A, Taha S, Shaath H, Bakhiet M. TNF-alpha and IL-8 in acute stroke and the modulation of these cytokines by antiplatelet agents. Curr Neurovasc Res. 2007;4:31–7.PubMedCrossRef
60.
go back to reference Kostulas N, Pelidou SH, Kivisakk P, Kostulas V, Link H. Increased IL-1beta, IL-8, and IL-17 mRNA expression in blood mononuclear cells observed in a prospective ischemic stroke study. Stroke. 1999;30:2174–9.PubMedCrossRef Kostulas N, Pelidou SH, Kivisakk P, Kostulas V, Link H. Increased IL-1beta, IL-8, and IL-17 mRNA expression in blood mononuclear cells observed in a prospective ischemic stroke study. Stroke. 1999;30:2174–9.PubMedCrossRef
61.
go back to reference Wittwer AJ, Carr LS, Zagorski J, Dolecki GJ, Crippes BA, De Larco JE. High-level expression of cytokine-induced neutrophil chemoattractant (CINC) by a metastatic rat cell line: purification and production of blocking antibodies. J Cell Physiol. 1993;156:421–7.PubMedCrossRef Wittwer AJ, Carr LS, Zagorski J, Dolecki GJ, Crippes BA, De Larco JE. High-level expression of cytokine-induced neutrophil chemoattractant (CINC) by a metastatic rat cell line: purification and production of blocking antibodies. J Cell Physiol. 1993;156:421–7.PubMedCrossRef
62.
go back to reference Yamasaki Y, Matsuo Y, Zagorski J, Matsuura N, Onodera H, Itoyama Y, et al. New therapeutic possibility of blocking cytokine-induced neutrophil chemoattractant on transient ischemic brain damage in rats. Brain Res. 1997;759:103–11.PubMedCrossRef Yamasaki Y, Matsuo Y, Zagorski J, Matsuura N, Onodera H, Itoyama Y, et al. New therapeutic possibility of blocking cytokine-induced neutrophil chemoattractant on transient ischemic brain damage in rats. Brain Res. 1997;759:103–11.PubMedCrossRef
63.
go back to reference Bachmann MF, Dyer MR. Therapeutic vaccination for chronic diseases: a new class of drugs in sight. Nat Rev Drug Discov. 2004;3:81–8.PubMedCrossRef Bachmann MF, Dyer MR. Therapeutic vaccination for chronic diseases: a new class of drugs in sight. Nat Rev Drug Discov. 2004;3:81–8.PubMedCrossRef
64.
go back to reference Buttini M, Appel K, Sauter A, Gebicke-Haerter PJ, Boddeke HW. Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat. Neuroscience. 1996;71:1–16.PubMedCrossRef Buttini M, Appel K, Sauter A, Gebicke-Haerter PJ, Boddeke HW. Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat. Neuroscience. 1996;71:1–16.PubMedCrossRef
65.
go back to reference Saito K, Suyama K, Nishida K, Sei Y, Basile AS. Early increases in TNF-alpha, IL-6 and IL-1 beta levels following transient cerebral ischemia in gerbil brain. Neurosci Lett. 1996;206:149–52.PubMedCrossRef Saito K, Suyama K, Nishida K, Sei Y, Basile AS. Early increases in TNF-alpha, IL-6 and IL-1 beta levels following transient cerebral ischemia in gerbil brain. Neurosci Lett. 1996;206:149–52.PubMedCrossRef
66.
go back to reference Lavine SD, Hofman FM, Zlokovic BV. Circulating antibody against tumor necrosis factor-alpha protects rat brain from reperfusion injury. J Cereb Blood Flow Metab. 1998;18:52–8.PubMedCrossRef Lavine SD, Hofman FM, Zlokovic BV. Circulating antibody against tumor necrosis factor-alpha protects rat brain from reperfusion injury. J Cereb Blood Flow Metab. 1998;18:52–8.PubMedCrossRef
67.
go back to reference Meistrell 3rd ME, Botchkina GI, Wang H, Di Santo E, Cockroft KM, Bloom O, et al. Tumor necrosis factor is a brain damaging cytokine in cerebral ischemia. Shock. 1997;8:341–8.PubMedCrossRef Meistrell 3rd ME, Botchkina GI, Wang H, Di Santo E, Cockroft KM, Bloom O, et al. Tumor necrosis factor is a brain damaging cytokine in cerebral ischemia. Shock. 1997;8:341–8.PubMedCrossRef
68.
go back to reference Martin-Villalba A, Hahne M, Kleber S, Vogel J, Falk W, Schenkel J, et al. Therapeutic neutralization of CD95-ligand and TNF attenuates brain damage in stroke. Cell Death Differ. 2001;8:679–86.PubMedCrossRef Martin-Villalba A, Hahne M, Kleber S, Vogel J, Falk W, Schenkel J, et al. Therapeutic neutralization of CD95-ligand and TNF attenuates brain damage in stroke. Cell Death Differ. 2001;8:679–86.PubMedCrossRef
69.
go back to reference Dalakas MC. High-dose intravenous immunoglobulin and serum viscosity: risk of precipitating thromboembolic events. Neurology. 1994;44:223–6.PubMedCrossRef Dalakas MC. High-dose intravenous immunoglobulin and serum viscosity: risk of precipitating thromboembolic events. Neurology. 1994;44:223–6.PubMedCrossRef
70.
go back to reference Cosimi AB, Conti D, Delmonico FL, Preffer FI, Wee SL, Rothlein R, et al. In vivo effects of monoclonal antibody to ICAM-1 (CD54) in nonhuman primates with renal allografts. J Immunol. 1990;144:4604–12.PubMed Cosimi AB, Conti D, Delmonico FL, Preffer FI, Wee SL, Rothlein R, et al. In vivo effects of monoclonal antibody to ICAM-1 (CD54) in nonhuman primates with renal allografts. J Immunol. 1990;144:4604–12.PubMed
71.
go back to reference Schneider D, Berrouschot J, Brandt T, Hacke W, Ferbert A, Norris SH, et al. Safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody): an open-label, dose escalation study in patients hospitalized for acute stroke. Eur Neurol. 1998;40:78–83.PubMedCrossRef Schneider D, Berrouschot J, Brandt T, Hacke W, Ferbert A, Norris SH, et al. Safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody): an open-label, dose escalation study in patients hospitalized for acute stroke. Eur Neurol. 1998;40:78–83.PubMedCrossRef
72.
go back to reference Furuya K, Takeda H, Azhar S, McCarron RM, Chen Y, Ruetzler CA, et al. Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study. Stroke. 2001;32:2665–74.PubMedCrossRef Furuya K, Takeda H, Azhar S, McCarron RM, Chen Y, Ruetzler CA, et al. Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study. Stroke. 2001;32:2665–74.PubMedCrossRef
73.
go back to reference Vuorte J, Lindsberg PJ, Kaste M, Meri S, Jansson SE, Rothlein R, et al. Anti-ICAM-1 monoclonal antibody R6.5 (Enlimomab) promotes activation of neutrophils in whole blood. J Immunol. 1999;162:2353–7.PubMed Vuorte J, Lindsberg PJ, Kaste M, Meri S, Jansson SE, Rothlein R, et al. Anti-ICAM-1 monoclonal antibody R6.5 (Enlimomab) promotes activation of neutrophils in whole blood. J Immunol. 1999;162:2353–7.PubMed
Metadata
Title
Therapeutic Antibodies in Stroke
Authors
Chye Yun Yu
Gandi Ng
Ping Liao
Publication date
01-10-2013
Publisher
Springer US
Published in
Translational Stroke Research / Issue 5/2013
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-013-0281-2

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