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Going Too Fast

A recent clinical trial for a cancer immunotherapy drug from the biotech company Incyte failed, surprising many observers. Since then, a new editorial in Science notes, three companies have canceled, suspended, or downsized 12 other phase III trials of the compound, epacadostat, or two similar drugs. The compounds were designed to block an enzyme called indoleamine (2,3)- dioxygenase (IDO), and therefore turn the immune system on cancer cells.

The problem may not be that IDO isn't a good way to turn the immune system on cancer, but rather that "the frenzy" over checkpoint inhibitors therapies "is outpacing the science," Science says. IDO may have been moved to clinical trials too fast, when not enough was known about how it works.

"The field still generally agrees that IDO makes sense to target, in combination with checkpoint inhibitors. Those drugs release a molecular brake on tumor-killing immune T cells. But the unleashed cells then stimulate the production of IDO, which, in a negative feedback loop, shuts them down again. IDO does this mainly by indirectly activating a protein inside immune cells called the aryl hydrocarbon receptor (AHR). Suppressing IDO should therefore make checkpoint inhibitors work better. But much about IDO remains unknown," according to the article. "Exactly how IDO stifles the immune system is unresolved, nor is it clear which immune cells are most involved." 

Indeed, experts are now agreeing that companies are beeing too agressive in moving into clinical trials with limited data, Science adds. The Incyte trial failure is an indication of that. But it also shouldn't wipe out all the enthusiasm about checkpoint inhibition and immunotherapy for cancer, which has shown success.