Reading biotechnologically produced drugs such as antibodies against cancer or rheumatism are apparently not as well tolerated as previously thought: they call the immune system on the scene, has now discovered a US research team. Responsible for this is a sugar variant, which is often grown during production to the active ingredients: Although it occurs in almost all mammals, but not in humans and is therefore recognized by the body as foreign. On the one hand, this can cause chronic inflammation and, on the other, it can weaken the effectiveness of the drugs because they are broken down more quickly by the immune system, the researchers write. But you already have a solution: Just add in the production of additional human sugar, which reduces the amount of animal sugar measurable. Practically all animal cells are equipped with various sugar molecules on their surface, which among other things allow them to come into contact with other cells. Some of them are identical in all mammals, but others differ from species to species. These include the so-called sialic acids: While most mammals use N-glycolylneuraminic acid? also called Gc variant? In humans, only the Ac variant, N-acetylneuraminic acid, is found in humans. However, people often come into contact with the Gc variant, such as when eating meat. It has long been assumed that this is not a problem because the immune system does not react to the sugar, reports co-author Ajit Varki. Meanwhile, we know that's not true: "We all develop antibodies against the Gc variant. However, this immune response varies greatly individually.
In people with a strong reaction, contact with the sugar could trigger an inflammatory response, Varki believes? which might explain why, for example, red meat is often associated with an increased risk of cancer. But some biotechnologically produced drugs can trigger such a reaction, the new study shows. In it, the researchers had investigated how human blood reacts, inter alia, to the cancer drug cetuximab. Like many growth factors, hormones and coagulation factors, it is produced by living cells and also contains Gc-sugar residues. They either come directly from production cells or from the feed medium, which often contains animal serum.
Varki and his team suspect that this defense reaction could be behind the sometimes immensely different effectiveness of the drugs in different people. The problem: It is currently impossible to completely avoid Gc contact in conventional production methods. However, the researchers have found a transitional solution: If the cell culture additionally added to the Ac variant in large quantities, it displaces a large part of the Gc residues in the drugs, and the immune response is much lower.
Darius Ghaderi (University of California, San Diego) et al .: Nature Biotechnology, online pre-publication, doi: 10.1038 / nbt.1651 ddp / science.de? Ilka Lehnen-Beyel advertisement