Trojan Horse to Fight Cancer - NAWA

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When asked about her discovery, Professor Magdalena Król says that she has a Trojan horse with armed warriors enter the tumour site. Armed with drugs, the warriors are supposed to reach those parts of solid tumours that no medications are currently able to penetrate. The discovery can become a turning point in oncological treatment.

PROFESSOR MAGDALENA KRÓL received a prestigious grant from the European Research Council (ERC) to continue her work. The studies are carried out under the project ‘Entrapment of hypoxic cancer by macrophages loaded with HAP’ at Warsaw University of Life Sciences (WULSSGGW) in close collaboration with the University of Warsaw and the Medical University of Warsaw. In 2017, the ERC listed Professor Król’s undertaking as one of ten most interesting projects financed by the Council in the course of its decade-long history. Professor Król established a start-up company Cellis in order to commercialise the discovery. This biotechnological company is developing a cell-based technology that might be used in the future for cancer treatment and diagnosis.

The ERC describes the projects that it finances as ‘high risk – high gain’. How high are the stakes for your project?

PROF. MAGDALENA KRÓL: The ERC reviewers described my project as ‘high risk – extremely high gain’. The project is very complex. It comprises many stages, at which something could go wrong, but if we obtain positive results at each stage, we have a chance to develop a new cell-based method of delivering drugs to solid tumours.

What makes this method innovative?

There are various systems of delivering drugs to the tumour. Scientists try to have the medications transported by metal nanoparticles, proteins or antibodies, but so far no researcher has managed to design a method where live cells are used to transfer the drug to the tumour site, to its most inaccessible parts.

How did you notice that this was possible?

When we look inside a neoplastic tumour, we can see that it is an autonomous being living in another organism. This autonomous area contains various types of cells, each of them playing a particular role at various stages of the tumour’s development. In order to grow, the tumour has to ensure a suitable growth of blood vessels. This is the area where we can currently deliver drugs. Yet tumours have certain avascular, that is inaccessible, regions, which are located far away from blood vessels (the cancer cells grow faster than new blood vessels can develop). These regions are highly hypoxic, that is deprived of oxygen. Even modern preparations used in anti-cancer therapy are not able to penetrate these regions. Thus, the cancer cells located there survive chemotherapy and are responsible for relapse or metastasis. From the physiological point of view, however, such hypoxia attracts macrophages, that is immune system cells, which induce the process of developing new blood vessels. And so we came up with the idea to use the macrophages to deliver the drugs to those inaccessible regions.

They are the Trojan horse?

In a way, yes. Since the macrophages naturally penetrate the tumour, we thought that – just as the Trojan horse helped hidden warriors enter Troy – the macrophages could transport anticancer drugs, that is our warriors, into the inaccessible regions of the tumour. However, we need to make sure that the drug delivered to the tumour site will be active. That is why we use appropriate protein structures which ensure that the drug is properly encapsulated. This package, in turn, is loaded into the macrophage, and the complete ‘Trojan horse’ is sent to the tumour site. The macrophages transfer their load to the cancer cells very quickly. It is a peculiar mechanism, a new discovery made by our team. We have called it TRAIN: TRAnsfer of Iron-binding proteiN. We are testing its application in diagnosing or treating other diseases.

What is the current stage of your project?

We are at the stage of preclinical trials. We are studying the TRAIN mechanism at the level of fundamental research and working on applying the results of in vitro and in vivo tests on mouse models to humanised models. We are trying to find out what groups of medications can be loaded using this mechanism so as to achieve the desired results at the tumour site.

Warsaw University of Life Sciences

Department of Cancer Biology, Institute of Biology