INTRABRAIN · Nanoplatforms and Oncolytic viruses for novel cancer immunotherapy strategies

Immunotherapy is a potential key weapon in the fight against cancer, in general, and Glioblastoma Multiforme (GBM), in particular. Still, a better understanding of how immunotherapy can be leveraged in GBM patients is direly needed. Disease complexity and blood-brain barrier impermeability mean that a standard vaccinology approach will not work. As part of a novel cancer management strategy, this project aims to create more efficacious vaccines using polymeric nanoparticles and self-assembled nanoplatforms in combination with modified oncolytic viruses. We will use biodegradable nanomaterials to protect the OV from body clearance and exploit the intranasal route for efficient delivery to the brain. We will incorporate the IL12 gene into a recombinant adenovirus vector backbone, which will stay under the nanoparticle protection until the drug reaches the tumour microenvironment and is released to reverse tumour-induced immunosuppression. This new strategy offers an efficient alternative to the current standard-of care - i.e. labour-intensive immunotherapy and possibly chemoradiation. The development of an off-the-shelf product, which provides additional anti-tumoral effects at different levels, would significantly prolong the life expectancy of GBM patients. This bioprocess would be scalable for production and compatible with Good Manufacturing Practices. The administration strategies, safety and efficacy of the anti-cancer agent will be validated in animal GBM models. The main training objective is to educate a strongly needed generation of interdisciplinary specialists in tight collaboration with large pharmacological industries, academia, and clinical centres. This will not only educate 14 outstanding early-stage researchers, but also greatly enhance their career perspectives through the unique opportunity to conduct transdisciplinary research and embark on a high-quality training in both academic and entrepreneurial industrial environments.