Researchers at Imperial College London have developed a test that uses cell combinations from a donor’s blood to predict whether drugs under development will lead to a severe immune reaction in humans. The new method could stave off disasters like the one that occurred in a 2006 clinical trial of a drug called TGN1412. In that instance, six healthy young men ended up in a hospital intensive care unit, suffering from multiple organ failure due to cytokine storm—a catastrophic inflammatory reaction.
Such reactions are a particular concern for new biological therapies, such as Herceptin and Avastin. They have the potential to cause severe reactions in humans that don’t happen in animal studies, making human cell testing important. However, it’s hard to predict cytokine storm reactions when just one cell type is tested, because it depends on the interaction of blood cells and endothelial cells. Before now, tests used endothelial cells taken from one donor’s vessels and white blood cells from another donor—which can cause the cells to have an immune reaction to each other, falsely suggesting a severe immune reaction for a drug that is actually safe. Imperial College London scientists isolated stem cells from the blood of one person, and then used them to grow endothelial cells in a petri dish. Next, they added white blood cells to the donor’s endothelial cells to create similar conditions to that found inside of blood vessels. Adding TGN1412 resulted in a cytokine storm, just as would happen inside of a person.
Because this technique only requires blood from one donor and does not mix cells from different people, it results in a more reliable test, the researchers said.
"As biological therapies become more mainstream, it's more likely that drugs being tested on humans for the first time will have unexpected and potentially catastrophic effects. We've used adult stem cell technology to develop a laboratory test that could prevent another disaster like the TGN1412 trial,” said study leader and professor Jane Mitchell, from the National Heart and Lung Institute at Imperial College London, in a prepared statement. "Drug companies have the technical capacity to start using this test now, but we're working on developing an off-the-shelf kit which will make it easy to use on a large scale."
This new method is also helpful because “personalized therapies can be tested to see how safe and effective they will be for an individual,” explained first study author Dr. Daniel Reed in a prepared statement.