UAntwerp researchers make breakthrough in fight against pancreatic and colorectal cancer

Tumours in the pancreas or colon are often shielded by a layer of connective tissue cells. This makes it difficult for medicines and radiation to reach the cancer cells. UAntwerp researchers have developed a new immune cell therapy that can destroy these connective tissue cells as well as the underlying cancer cells, improving treatment outcomes.

There is a great need to improve treatment outcomes for pancreatic cancer and advanced colorectal cancer. These types of cancers usually do not respond well to treatment because the tumour cells are shielded by connective tissue cells, called cancer-associated fibroblasts. A subset of these connective tissue cells contributes to the aggressiveness of these cancers, making them more deadly. Researchers from Professor Evelien Smits' team at UAntwerp have discovered that cancer cells and these connective tissue cells shielding them both carry the molecule 'CD70' on the outside. With the support of Kom op tegen Kanker, they have developed a new immune cell therapy that targets this molecule.

Cell therapy with natural killer cells

This new cell therapy consists of so-called natural killer cells.  'Natural killer cells are the special forces of our immune system, which can recognise and destroy cancer cells', says PhD student Astrid Van den Eynde, who conducted the research. 'This makes them the ideal immune cells to fight cancer.'

The researchers have modified natural killer cells in the laboratory to target cancer cells more effectively. 'We have equipped the natural killer cells with a so-called chimeric antigen receptor, or CAR for short. This CAR is an extra gripping arm that specifically recognises the CD70 molecule on cancer cells and connective tissue cells', Van den Eynde says. 'Our laboratory tests have shown that these modified natural killer cells recognise and destroy the right cells in the tumour.'

The results of the study were recently published in the prestigious Journal of Hematology & Oncology.

A potentially safer and cheaper alternative to CAR-T cells

The new cell therapy joins a group of immunotherapies that many scientists have high hopes for. Indeed, adding a CAR molecule as a gripping arm to immune cells has been done before, but with T cells. T cells are immune cells that can also destroy cancer cells. This CAR-T cell therapy has already achieved very good results in patients with certain types of blood cancer. Researchers are working to further improve this therapy, because serious complications can occur and it is not very effective against solid tumours. 'Natural killer cells are potentially safer than CAR-T cells', says Dr Jonas Van Audenaerde, cell therapy specialist and member of Professor Smits' team. 'The first clinical studies with these cells showed hardly any side effects for the patient. Moreover, we can produce these cells on a large scale from the blood of healthy donors, in contrast to CAR-T cells, which have to be made from the patient's own blood.'

'This means that we can produce a large quantity of CAR natural killer cells at once, so that they are always immediately available to patients when they need them', says Van Audenaerde. 'This also reduces the cost per treatment.' As a next step, the researchers — again with the support of Kom op tegen Kanker — are preparing the new immune cell therapy for testing in clinical trials and are investigating in the laboratory whether other cancer types could also be treated with it.

David Vansteenbrugge, managing director of Kom op tegen Kanker: 'The natural killer cells developed by Prof. Smits' team sound very promising. We are very pleased that we were able to help fund this research. With our project funding, we want to ensure that this new treatment actually reaches patients. The follow-up research focuses on the preparatory work needed to administer this therapy to patients in clinical trials. This is very important, because every patient deserves the best possible treatment.'