Medicines are produced under strict conditions. However, every so often something that is not supposed to be in there, such as a bacteria or fungus, can contaminate the product. This may have serious effects on the patient’s health or well-being. Therefore, medicines need to be tested prior to release into the market. Sanquin researchers have devised an alternative way to test medicines for the presence of these dangerous contaminants: using immune cells from donor blood. By doing so, the use of test animals, mostly rabbits, can be avoided.
Blood cells can detect intruders
Everyone has cells called monocytes in their blood: they form an essential part of your immune system. If your immune system encounters something that doesn’t naturally belong in your body, such as foreign bacteria, the monocytes will fight them and produce substances to help kill the intruder. These substances, called cytokines, help you fight the intruder but are also responsible for the fever you typically get upon infection.
Monocytes derived from donor blood can also release these substances outside of the human body in a test tube. When you expose these monocytes to a medicine, they will detect whether there is a pathogen in it. When the monocytes detect a pathogen, cytokines will be released and a color reaction will occur. Therefore, this test is called the Monocyte Activation Test (MAT).
Testing human medicines on human cells
“Our MAT mimics the human body very well,” says Sanquin Diagnostic Services’ senior scientist Marijke Molenaar. “The MAT is accepted as a replacement for a rabbit-based pyrogen test in Europe. The rabbit pyrogen test will be banned by the European Pharmacopoeia from 2026 onwards and in principle needs to be replaced with the MAT since both assays detect a broad range of pyrogens.
This path saves the lives of many rabbits and importantly, since humans have slightly different immune reactions than rabbits, results in a better test.”
Sanquin requests specific donors to donate blood for isolation of the monocytes for the MAT. The cells are processed as quickly as possible so that they do not lose their responsiveness. “We put the cells of four donors together in the test, because of the differences between peoples’ immune systems. The immune cells of one donor can react just a little faster than those of another.” Marijke explains.
Sanquin is a center of expertise and one of the founders of the MAT, thanks to its unique proximity and collaboration between different partners involved in the process; Sanquin Bloodbank (selection of specific donors), Sanquin Research (with in-depth knowledge of the immune system), Essange Reagents, (who isolates and stores the cells), and Sanquin Diagnostic Services. Sanquin Diagnostic Services carries out the MAT for various pharmaceutical manufacturers. Moreover, Marijke and her colleagues hardly ever find a contamination. “Maybe one in a thousand times,” she says. “That’s a good thing because you want medicines to be as safe as possible. We are very pleased that we can contribute to medical safety without the unnecessary suffering and death of test animals.”