Healthy Skepticism Library item: 5893

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Publication type: news

Suntharalingam G, Et AL.
Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412
New England Journal of Medicine ( NEJM ) 2006 Aug 14
http://content.nejm.org/cgi/content/short/NEJMoa063842

Full text:

Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody
TGN1412

http://content.nejm.org/cgi/content/short/NEJMoa063842

Ganesh Suntharalingam, F.R.C.A., Meghan R. Perry, M.R.C.P., Stephen
Ward, F.R.C.A., Stephen J. Brett, M.D., Andrew Castello-Cortes,
F.R.C.A., Michael D. Brunner, F.R.C.A., and Nicki Panoskaltsis, M.D., Ph.D.

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.