Off-Target Platelet Activation in Macaques Unique to a Therapeutic Monoclonal Antibody

AMG X, a human neutralizing monoclonal antibody (mAb) against a soluble human protein, caused thrombocytopenia, platelet activation, reduced mean arterial pressure, and transient loss of consciousness in cynomolgus monkeys after first intravenous administration. In vitro, AMG X induced activation in...

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Veröffentlicht in:	Toxicologic pathology 2012-08, Vol.40 (6), p.899-917
Hauptverfasser:	Santostefano, Michael J., Kirchner, Jacqueline, Vissinga, Christine, Fort, Madeline, Lear, Sean, Pan, Wei-Jian, Prince, Peter J., Hensley, Kelly M., Tran, Duc, Rock, Dan, Vargas, Hugo M., Narayanan, Padma, Jawando, Remi, Rees, William, Reindel, James F., Reynhardt, Kai, Everds, Nancy
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Intravenous Animals Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - metabolism Antibodies, Monoclonal - pharmacokinetics Antibodies, Monoclonal - toxicity Biological and medical sciences Blood Platelets - drug effects Blood Platelets - metabolism Cynomolgus Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Hematologic and hematopoietic diseases Humans Hypotension - blood Hypotension - chemically induced Immunoglobulin Fab Fragments - metabolism Immunoglobulin Fc Fragments - metabolism Macaca Macaca fascicularis Male Medical sciences Nervous system (semeiology, syndromes) Neurology Papio Platelet Activation - drug effects Platelet Aggregation - drug effects Platelet diseases and coagulopathies Protein Binding Serotonin - metabolism Syncope - blood Syncope - chemically induced Thrombocytopenia - blood Thrombocytopenia - chemically induced Thromboxane B2 - metabolism Toxicology
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