Photo by Juan D. Alfonso
Scientists have developed a test that uses cells from a single donor’s blood to predict whether a new drug will cause a cytokine storm.
The group says this is an improvement over current tests, which use endothelial cells and peripheral blood mononuclear cells (PBMCs) from two separate donors and can therefore produce inaccurate results.
Furthermore, current tests cannot differentiate drugs that induce a mild cytokine storm from those that induce a severe one, but the new test can.
Jane Mitchell, PhD, of the National Heart and Lung Institute at Imperial College London in the UK, and her colleagues described the new test in The FASEB Journal.
Current tests for cytokine storm reactions use endothelial cells taken from the vessels of one donor and PBMCs from a different donor because endothelial cells are normally only grown from tissue removed in surgery or post-mortem, or from umbilical vessels after birth.
When cells from two different donors are used, one may have an immune reaction to the other. And this can result in the test falsely showing a severe immune reaction to a drug that is safe.
Dr Mitchell and her colleagues say they have solved this problem by isolating stem cells from the blood of a volunteer and using them to grow endothelial cells in a dish. The team then added PBMCs to the donor’s own endothelial cells to recreate the unique conditions found in their blood vessels.
When the scientists added the immunomodulatory drug TGN1412, the mixture of cells released a cytokine storm, as would happen inside the human body.
Responses to other drugs were consistent with those observed in humans as well. There was a modest response to alemtuzumab (Campath) and no response to the control antibodies trastuzumab (Herceptin), bevacizumab (Avastin), and ofatumumab (Arzerra).
“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,” Dr Mitchell said.
“We’ve used adult stem cell technology to develop a laboratory test that could prevent another disaster like the TGN1412 trial [in which 6 healthy young men developed multi-organ failure]. 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.”
The team has collaborated with the National Institute for Biological Standards and Control to validate the test and are now working with the clinical trials company Quintiles to develop the technology further.
