3Rs: Reduction / Replacement: New test could weed out dangerous drug trials

The makers of a new test think that their approach might have provided a warning of risks to the six volunteers in the TGN1412 trial who nearly lost their lives. The utility of the lethal experiments in macaques - or lack thereof - wasn't a major theme here, but it was mentioned.

If there is, in fact, a test that can help predict the safety of anitbodies and other high-risk drug candidates, I'd say this question isn't whether it should be used, but when. Done in advance of experiments that kill countless animals, we wouldn't just save lives, we'd save millions invested in drug candidates that aren't fit for use.

http://www.nature.com/news/2006/061204/full/061204-13.html:

"The victims of the TGN1412 disaster suffered a 'cytokine storm', featuring massive release of inflammatory molecules called cytokines, and overproliferation of immune cells known as CD4 cells. In Inglis's studies, this effect could only be reproduced when the TGN1412 antibodies were dried onto the surface of an experimental vessel before being presented with human immune cells, rather than floating in solution as in usual preclinical toxicity tests. Antibodies that are dried and stuck to a surface are often more active.

It is not entirely clear why the drug produced such devastating effects in humans but not in macaques, which possess an almost identical receptor protein for the antibody. But using antibody-immobilization tests such as the one developed by Inglis could help to identify potential dangers not flagged up by animal tests.

'If I were developing a drug of this kind in the future, I would take these tests seriously,' Inglis said at the unveiling of the expert group's report. 'I would hope they become standard in future.' He and his colleagues are preparing to publish details of the test in a scientific journal."
[Emphasis added]

Prior posts on TGN1412:
Drug rules should change
Drug trial victim has cancer
What the hell happened?