Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412
- PMID: 16908486
- DOI: 10.1056/NEJMoa063842
Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412
Abstract
Six healthy young male volunteers at a contract research organization were enrolled in the first phase 1 clinical trial of TGN1412, a novel superagonist anti-CD28 monoclonal antibody that directly stimulates T cells. Within 90 minutes after receiving a single intravenous dose of the drug, all six volunteers had a systemic inflammatory response characterized by a rapid induction of proinflammatory cytokines and accompanied by headache, myalgias, nausea, diarrhea, erythema, vasodilatation, and hypotension. Within 12 to 16 hours after infusion, they became critically ill, with pulmonary infiltrates and lung injury, renal failure, and disseminated intravascular coagulation. Severe and unexpected depletion of lymphocytes and monocytes occurred within 24 hours after infusion. All six patients were transferred to the care of the authors at an intensive care unit at a public hospital, where they received intensive cardiopulmonary support (including dialysis), high-dose methylprednisolone, and an anti-interleukin-2 receptor antagonist antibody. Prolonged cardiovascular shock and acute respiratory distress syndrome developed in two patients, who required intensive organ support for 8 and 16 days. Despite evidence of the multiple cytokine-release syndrome, all six patients survived. Documentation of the clinical course occurring over the 30 days after infusion offers insight into the systemic inflammatory response syndrome in the absence of contaminating pathogens, endotoxin, or underlying disease.
Copyright 2006 Massachusetts Medical Society.
Comment in
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T-cell costimulation--biology, therapeutic potential, and challenges.N Engl J Med. 2006 Sep 7;355(10):973-5. doi: 10.1056/NEJMp068087. Epub 2006 Aug 14. N Engl J Med. 2006. PMID: 16908487 No abstract available.
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Volunteers at risk.N Engl J Med. 2006 Sep 7;355(10):1060-1. doi: 10.1056/NEJMe068175. Epub 2006 Aug 14. N Engl J Med. 2006. PMID: 16908488 No abstract available.
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Cytokine storm and an anti-CD28 monoclonal antibody.N Engl J Med. 2006 Dec 14;355(24):2592-3; author reply 2593-4. doi: 10.1056/NEJMc062750. N Engl J Med. 2006. PMID: 17167145 No abstract available.
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Cytokine storm and an anti-CD28 monoclonal antibody.N Engl J Med. 2006 Dec 14;355(24):2593; author reply 2593-4. N Engl J Med. 2006. PMID: 17167937 No abstract available.
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Cytokine storm and an anti-CD28 monoclonal antibody.N Engl J Med. 2006 Dec 14;355(24):2591-2; author reply 2593-4. N Engl J Med. 2006. PMID: 17171819 No abstract available.
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Cytokine storm and an anti-CD28 monoclonal antibody.N Engl J Med. 2006 Dec 14;355(24):2592; author reply 2593-4. N Engl J Med. 2006. PMID: 17171820 No abstract available.
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Cytokine storm and an anti-CD28 monoclonal antibody.N Engl J Med. 2006 Dec 14;355(24):2593; author reply 2593-4. N Engl J Med. 2006. PMID: 17171821 No abstract available.
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