Medicine Small gene variants can render antibody therapies ineffective
A tiny deviation in the genome can render expensive cancer drugs useless. As researchers from the University of Basel show in a new study, even the smallest genetic differences can render antibody therapies ineffective.
18.12.2025, 06:01
SDA
This is because they prevent the drugs from binding to their target, as a study published on Wednesday evening in the journal "Science Translational Medicine" shows. The scientists see their discovery as a possible explanation as to why some patients do not respond to antibody therapy.
Antibody-based therapies are used for many diseases. Antibodies recognize very specific structures and bind to them. For example, they can deliver active substances to exactly the right target structure in the body.
The proportion of patients in whom such a variant occurs and prevents the effectiveness of the therapy is relatively small, emphasized the University of Basel in a press release on the study. Nevertheless, the researchers argue in the study that genetic diversity should be given greater consideration in drug development. "It is important that doctors think about this aspect when a therapy does not work," study author Lukas Jeker was quoted as saying in the press release.
In future, genetic tests could help to select the right therapy for individuals and avoid ineffective treatments with sometimes severe side effects.
87 antibodies examined
For the study, the research team analyzed 87 different therapeutic antibodies. For almost all of them, they found natural gene variants in the target regions of the proteins to which the antibodies are supposed to bind. These binding sites, called epitopes, are crucial for the function of the drugs. A change in just a single amino acid at this site can prevent the antibody from binding and thus lead to primary resistance.
The results also showed that different drugs that are directed at the same target protein can be affected differently by the gene variants. For example, there are variants that block one drug but not an alternative drug.
