‘Nanobodies’ herald a new era in cancer therapy

Cancer, along with heart and vascular disease, is the major cause of death in the Western world. The first generation of anti-cancer drugs has already saved many lives, but because these medicines are non-specific they also often have severe side effects. Researchers at VIB (the Flanders Interuniversity Institute for Biotechnology) are now developing ‘nanobodies’ − a new generation of drugs consisting of extremely small antibodies that target tumour cells very specifically.

The vast majority of the current medicines for treating tumours − the so-called chemotherapeutics − are seldom specific. Indeed, because a chemotherapy treatment is not only toxic to cancer cells but to the body’s normal cells as well, patients often experience severe side effects. The VIB research team under the direction of Hilde Revets and Patrick De Baetselier (Department of Molecular and Cellular Interactions, Free University of Brussels) is searching − successfully − for new, specific, effective cancer therapies.

For several years now, the leading strategy in the treatment of cancer has been based on the production of antibodies, which are protective substances produced in the organism to defend against intruding foreign bodies − protecting us against infections arising from bacteria and viruses. Antibodies can also react with tumour-specific substances that appear only on the cancer cell membrane. These ingenious antibodies seek out and bind very specifically to the cancer cells. As a result, the tumour is removed in a highly targeted, specific manner. At the moment, ten such medicines are available to patients. But even though these antibody medicines are a good step in the right direction, there is clearly room for improvement. The antibodies that are being used are large proteins that have difficulty penetrating tumours. In addition, their complex structure makes large-scale production very difficult and expensive.

In order to cope with these problems, the VIB researchers are using camel antibodies. Extremely small compared to conventional antibodies, this unique class of antibodies has been renamed ‘nanobodies’. Having all the advantages of the conventional antibodies, nanobodies also have several more important characteristics: they are small and they keep their tumour-specific character. At the same time, they are very stable, soluble proteins that are much easier and less expensive to produce than conventional antibodies. So, researchers have recently begun to evaluate nanobodies as anti-cancer medicines. The first results look promising: in experiments conducted on mice, a tumour with a certain protein on its membrane was successfully counteracted through administration of a nanobody directed against this protein.

To translate these results into a possible application for humans, VIB is collaborating with Ablynx, a company established by VIB and GIMV in 2001 with the aim of marketing the nanobody technology. Today, Ablynx has already developed nanobodies against 16 different therapeutic targets that represent a wide range of diseases in humans. Two of these nanobodies are in the pre-clinical phase and, according to plan, will be ready to be clinically tested next year.

These recent results are a new step toward the development of medicines based on nanobodies. In addition to cancer, other life-threatening diseases − such as certain inflammatory diseases, or heart and vascular diseases − are possibly eligible for a medical treatment with nanobodies.