One of the main goals of InveNNta is to develop new diagnostics systems and monitor cancer cells in vivo. In order to do that, the Traslational Medical Oncology group of the Health Research Institute of Santiago de Compostela (IDIS), in cooperation with researchers from the International Iberian Nanotechnology Laboratory (INL), is participating in the development of a magnetoresistive platform for the detection of Circulating Tumour Cells (CTC).

Doctor Clotilde Costa, one of the main researchers in this team, points out versatility, high sensitivity and precision as the main advancements of this technology, as it allows for the use of different and more specific markers in order to identify subsets of tumour cells in the blood.

“The main advantage is that it’s not limited to EpCAM expressing CTCs, but we can also include other markers with less epithelial phenotypes and, in doing so, recognize a subset of CTCs that current systems don’t take into account”, she explains. (EpCAM is an adhesion molecule located on the surface of epithelial cells and is generally used to distinguish tumour cells from blood cells).

 

Operation and cell characterization

The way the platform operates is based on the detection of magnetic nanoparticles attached to tumour cells. Blood samples are previously incubated with these nanoparticles, covered with an antibody that facilitates it’s adhesion to CTCs. When they pass through the sensor, the platform detects the nanoparticles’ magnetic charge and turns it in to an electrical signal meaning that a tumour cell was detected.

From this moment on the Traslational Medical Oncology group’s involvement takes on significant importance, as they are responsible for the biological characterization of CTCs through tumour cell lines and the selection of markers used in nanoparticles for their isolation. “When tumour cells detach from the primary tumour and enter the bloodstream they change their expression of membrane markers as well as their morphology. They lose epithelial cell characteristics and acquire mesenchymal stem cell properties”, says Dr Costa emphasising the importance of considering these changes when functionalising nanoparticles in order to bind them with certain types of CTCs.

 

Cell culture to investigate new therapeutic targets

At the same time, they are trying to culture isolated CTCs in order to improve their cellular and molecular characterization. This work is paramount in order to identify potential therapeutic targets. This is another great advantage of using nanoparticles. “Isolated cells are viable and grow in culture, whereas most CTC detection systems require previous fixation steps that kill the cell”, says the researcher.

Clotilde Costa postulates this system as an “alternative to Veridex, currently the only one approved by the Food and Drug Administration (FDA)”. In addition, since it is a small device with a portable design it can be used to monitor the patient’s evolution in real time. It would even be possible to go one step further and adapt the platform to a continuous flow system (apheresis) that could sample more blood from the patient and even remove circulating tumour cells.

Thirteen researchers from the Traslational Medical Oncology group are involved in InveNNta, a cooperation that, in Dr. Clotilde Costa’s words, has given them “the opportunity to work with a multidisciplinary team offering different approaches towards common goals and also the opportunity to have INL’s entire infrastructure at their disposal”.