Your News story “Can super-antibody drugs be tamed?” (Nature 440, 855–856; 2006), on the TGN1412 anti-CD28 antibody drug and the fallout from this near-fatal clinical trial, lacks a simple interpretation of the data based on common sense.
Accounts of the clinical trial describe how, following intravenous infusion of the antibody, the volunteers were clawing off their clothes, swelling with obvious oedema, and starting to suffer pain and panic within minutes. The developer of TGN1412, Thomas Hunig, links this disabling “cytokine storm” to T-cell activation. But such a reaction would take hours.
In fact, these volunteers could have been victims of the release of preformed mediators, of the types usually found within the granules of cells of an allergic response. As any subject of an anaphylactic response can testify — myself included — the response is immediate, with similar symptoms to those experienced by the volunteers in the TGN1412 trial.
The literature suggests that CD28 can be expressed by cells of the allergic response (M. Tashiro et al. J. Immunol. 158, 2382–2389; 1997), and the real disaster was that no tests were carried out for the possibility of allergic reactions before TGN1412 was released into the blood stream. A simple ‘weal and flare’ allergic-response test could have easily alerted the clinicians to a potential allergic reaction. But reports have suggested that no such tests were performed. The first human trial with this drug was the intravenous infusion that led to such catastrophic responses in these volunteers.
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Nature Reviews Immunology (2010)