Therapeutic exosomes as novel treatment for ovarian cancer

End of project summary

Background

• Cells are able to secrete vesicles called exosomes to transfer specific information from donor cells to target cells, leading to the reprogramming of the recipient cells.
• Exosomes derived from healthy cells are involved in physiological process including inhibition of cancer cell growth whereas exosomes derived from tumour cells are implicated in pathological processes and can be used for the detection and monitoring of disease.
• In ovarian cancer (OC), characterised by poor prognosis and lack of biomarkers of disease, exosomes mediate cancer growth, metastasis and resistance to chemotherapy hence we decided to characterise OC exosomes to assess their biomarker potential. In contrast, non-tumour derived (therapeutic) exosomes were evaluated to determine therapeutic potential.

Main findings

• Optimisation of exosome’s purification and characterisation tools using cisplatin resistant and sensitive OC cell lines and clinical samples. Impact: validation of protocols and new techniques for exosome research and drug development.
• In vitro models to study ovarian cancer disease influence exosome secretion and cargo with exosomes from cells grown as tumour spheroids containing similar cargo exosomes from clinical samples. Impact: In preclinical drug development, biomarker discovery and reduction of animal experimentation by using tumour spheroids to de-risk the development of therapeutic and biomarker exosomes.
• Exosomes derived from ovarian and peritoneal cells, ascites fluid and serum samples from OC patients are significantly different in terms of morphologically, surface markers, uptake potential and cargo from exosomes secreted from ovarian and serum samples isolated from healthy patients. Clinical and Drug development Impact: The RNA cargo of exosomes from OC patients can be used as biomarker of disease. Potential to use exosome fractions with best uptake capacity to carry chemotherapeutic drugs to increase therapeutic efficacy.
• Identification of a lead fraction of therapeutic exosomes effective at killing OC cells including cisplatin resistant OC cells. Impact: Potential to be developed as new treatment option for OC patients. This may improve survival when current treatments have stopped working and improve quality of life of cancer patients and their families.