Single donor's blood cells to test side effects of drugs

UK researchers are using combinations of cells from a single donor’s blood to predict whether a new drug will cause a severe immune reaction in humans. The test aims to avert disasters like the 2006 trial of the drug TGN1412, which resulted in six healthy young men experiencing multiple organ failure following an inflammatory reaction called a cytokine storm.

Biological therapies, such as the cancer drugs Herceptin and Avastin, utilise biological material such as antibodies. Because the medicines are specific to humans, severe reactions will not materialise in animal studies; tests on human cells are therefore essential. But cytokine storm side effects are hard to predict with tests where just one cell type is used, since they depend on interactions between blood cells and endothelial cells, which form the lining of blood vessels.

Endothelial cells are found deep within the body, so they are normally only grown from tissue removed in surgery, post mortem or from umbilical vessels after birth. Current tests use endothelial cells taken from vessels of one donor and white blood cells from a different donor; however, when cells from two different donors are used, one may have an immune reaction to the other. This means the system is already primed for inflammation before the drug is added and can result in the test falsely showing a severe immune reaction to a safe or mild drug.

A research team from Imperial College London isolated stem cells from the blood of a volunteer and used them to grow endothelial cells in a dish. They then took white blood cells which they added to the donor’s own endothelial cells to recreate the conditions found in their blood vessels. When TGN1412 was added to the test tube, the mixture of cells released a cytokine storm, as would happen inside the body.

Writing in The FASEB Journal, the researchers noted that the use of a single donor means the test can be utilised for the development of personalised medicine. First author Dr Daniel Reed explained that “personalised therapies can be tested to see how safe and effective they will be for an individual”.

The researchers have 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. Study leader Professor Jane Mitchell revealed, “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.”

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