Project: LDL-like nanoparticles for CAR-T-based glioblastoma immunotherapy

Acronym	ECM-CART (Reference Number: EURONANOMED2021-113)
Duration	01/01/2022 - 31/12/2024
Project Topic	This project aims to demonstrate that the targeted delivery of exogenous antigens to the extracellular matrix (ECM) of brain tumors provides a safe and specific target for chimeric antigen receptor T-cell (CART) for the treatment of glioblastoma (GBM). GBM is the most common brain tumor in adults and despite all the advances combining surgery, chemotherapy and radiotherapy, it is still a disease with no cure. CART therapy is one of the most promising approaches in the treatment of GBM. The main obstacle limiting CART efficacy is the scarcity of highly expressed tumor antigens in GBM. In this regard, the ECM could provide a niche for abundant antigens suitable for activating CART; nonetheless, as these antigens are also present in healthy tissues, including the brain, a direct target by CART would lead to severe side effects. In this project, we hypothesize that the components of the ECM could become ideal targets for CART therapy if labelled with FITC-peptides, enabling a tumor treatment using CART directed to FITC (FITC-CART). Therefore, we propose to deliver FITC-peptides to the ECM by incorporating these conjugates in small nanoparticles that mimic low-density lipoproteins (LDLNP), taking advantage of the known capacity of LDL to accumulate into brain tumors. The nanoparticle-based delivery of exogenous antigens will promote local accumulation of antigens in the tumor avoiding unspecific antigen build-up in healthy organs, which will result in the activation of CART only at the ECM of brain tumors. This project describes an original approach for the treatment of GBM using CART therapy. Building upon the collective expertise of the consortium, this project will 1) Identify new peptides with selective affinity for the ECM of brain tumors; 2) synthesize FITC-peptide loaded LDLNP 3) deliver and release the FITC-peptides at the tumor ECM 4) produce and deliver FITC-CART to ECM 5) study the efficacy of the CART activated by FITC-peptides in GBM animal models.
Website	visit project website
Network	EuroNanoMed III
Call	Joint Transnational Call (2021)

Project partner

Number	Name	Role	Country
1	Health Research Institute of Santiago de Compostela	Coordinator	Spain
2	Tel Aviv Sourasky Medical Center	Partner	Israel
3	GalChimia S.A.	Partner	Spain
4	Tel Aviv University	Partner	Israel
5	University of Tartu	Partner	Estonia