Introduction

The patent is based on extracellular vesicles (EV) capable of counteracting the migration of tumour cells, in particular of gliobastoma. This discovery is relevant for the development of a targeted therapeutic approach against tumor infiltration and metastatisation, improving the prognosis of patients. Surprisingly, such vesicles were isolated from human teratocarcinoma cells. Even more surprisingly, the antimigratory effect is associated to the CRIPTO oncoprotein on the surface of the vesicles.

Technical features

Extracellular vesicles (EVs) are structures encapsulated in lipid membranes, released from cells and filled with bioactive components. They are able to travel in body fluids, cross the blood-brain barrier and transport molecules away from the cells of origin, inducing specific responses in the target cells. Due to their unique characteristics, EVs are in the limelight as promising anti-cancer therapeutic agents.
For the first time, small and large EVs were isolated and characterized from teratocarcinoma cells and their effect on glioblastoma cells was analyzed by cell migration, proliferation and chemotherapy resistance assays. The results showed the inhibitory effect of large EVs on tumor cell migration, without inducing undesirable effects such as increased cell proliferation or resistance to chemotherapy. The CRIPTO protein, implicated in embryogenesis and tumorigenesis processes, was found to be associated with teratocarcinoma vesicles and to have an antimigratory effect on glioblastoma.
TRL of the invention is 3. Preclinical studies are planned both in vivo in mouse models of glioblastoma and in culture on other tumor types.

Possible Applications

• Therapeutic approaches for the treatment of glioblastoma;
• Therapeutic approaches for the treatment of aggressive, invasive and metastatic tumors (i.e. colon and breast cancer, melanoma);
• Inhibition of metastases.

Advantages

• Identified EVs exhibit antitumour activity per se without the need for further modification;
• Tumor vesicles recognise and accumulate more readily in tumour tissue in vivo;
• Tumour vesicles cross the blood-brain barrier more easily;
• A molecule (CRIPTO) involved in the observed antimigratory effect has been identified.