LUNGEVs (Extracellular Vesicles to fight against Lung Cancer)

Lung cancer is the 2nd most prevalent cancer globally (2 million new cases in 2020), 85% of them affected by non-small cell lung cancer (NSCL), with 150,000 deaths yearly Lin Europe. Standard-of-care (SoC) consisting of chemotherapy combined with radiotherapy, or even surgeries are not effective, since the 5-year survival rate is below 20%.

Novel therapies (i.e. immunotherapies) have shown some improvement, but still are considered not efficient at all. Among them, mRNA vaccines have shown more relevant results. mRNA vaccines target immature dendritic cells (iDC) to activate them by transfecting tumour associated antigens mRNAs (TAA). Then mature DC, efficient antigen-presenting cells, trigger the immune cascade (i.e. CD8+ and CD4+ effector T lymphocytes) that detects TAA and supresses tumour cells.

The efficiency of mRNA vaccines is still limited by the mRNA nanocarrier delivery systems (based on polymers, lipids, or viral vectors). Current delivery nanocarriers are not yet suitable for all treatments, because side effects are triggered since nanocarriers are recognized as foreign entities by the immune system. Extracellular Vesicles (EVs) are of natural origin with potential use as a novel delivery system. EVs escape from the immune system and show prevalence for specific cells. For this reason, EVs would be produced using JAWSII, an iDC cell line.

However, EVs technology is not ready to be transferred for therapeutical applications, due to the limitations detected: EVs manufacturing platform, purification and RNA loading. LUNGEVs is focused to overcome such limitations, using mRNA vaccine against NSCLC as specific application.

– Manufacturing. All components have to be GMP compliant (e.g. Animal derived component free media), and all solutions proposed scalable. We propose the development of high productive platform based on perfusion cultures.
– Purification. Cells engineered to produced novel improved EVs (EVs displaying a moiety to ease the purification) in a single scalable step.
– Increase EVs loading with a combination of active loading techniques together with the use of surfactants.

LUNGEV is a research Project funded by AGAUR (Industria del Coneixement, Llavor) with reference 2021 LLAV 00042.