Project: Reactivation of antitumor immune responses in gliomas using nanotechnology based targeted delivery

Acronym	iNANOGUN (Reference Number: EURONANOMED2020-071)
Duration	01/01/2021 - 01/01/2024
Project Topic	Glioblastoma (GBM) is the most common and aggressive brain cancer, for which the current therapy is not effective. Cancer progression is associated with disabling host immunity. Immunotherapy using immune checkpoint inhibitors (CPI) aims to restore antitumor response and is a revolutionary approach to eradicate cancer. However, GBM patients respond poorly to CPI as GBM is immunologically a “cold” tumor with low infiltration of functional T and natural killer (NK) cells. Tumor-associated myeloid cells largely contribute to this “cold” GBM microenvironment. We propose to develop smart nanosystems to deliver immunomodulatory agents to reactivate antitumor responses in GBM and sensitize this tumor to CPI. Specifically, in this project, we will develop innovative nanosystems to deliver small interfering RNA (siRNA): 1) to revive cytolytic activities of NK cells, and 2) to modify tumor-associated myeloid cells by blocking their pro-tumoral polarization and immunosuppressive functions. As the nanosystems, the consortium will develop liposome, polymersome and dendrimer nanoformulations functionalized with homing peptides for effective crossing of the blood-brain barrier and specific targeting of immune cells in the tumor microenvironment. The nanosystems will be evaluated for their ability to deliver siRNAs and immunomodulatory activity both in vitro and in vivo. The most promising candidate nanosystems will be tested in combination with CPI for anti-GBM activity in clinically relevant models in mice. The success of this project will provide a proof-of-concept for therapeutic awakening of the GBM microenvironment using therapeutic siRNAs and deliver a smart immunomodulatory nanosystem for subsequent Investigational New Drug-enabling preclinical, scale-up, and regulatory studies. It will also generate clinically relevant Intellectual Property, as well as data of general interest for the cancer research community on novel strategies to fight CPI resistance in other cancers.
Network	EuroNanoMed III
Call	Joint Transnational Call (2020)

Project partner

Number	Name	Role	Country
1	Nencki Institute of Experimental Biology, Polish Academy of Sciences	Coordinator	Poland
2	OncoArendi Therapeutics S.A.	Partner	Poland
3	Centre National de Recherche Scientifique (CNRS)	Partner	France
4	University of Tartu	Partner	Estonia
5	Cellvax SAS	Partner	France
6	IRCCS Neuromed	Partner	Italy