Project: Cationic Gold nanoparticles mediated mRNA cytoplasmatic-targeted delivery for production of CAR-T lymphocytes for Chronic Lymphoid Leukemia immunotherapy

Acronym CONCORD (Reference Number: JTC2018-023)
Duration 01/06/2019 - 31/12/2022
Project Topic CAR T cell therapy is a type of immunotherapy based in the ex-vivo engineering of patient T-lymphocytes to produce special receptors on their surface called chimeric antigen receptors (CARs) that target the T-lymphocytes specifically towards the tumour when reintroduced in the patient. CAR T cell therapy targeting CD19 is showing very promising results with recurrent and refractory chronic lymphocytic leukaemia. However, since today’s CAR T lymphocytes stay active indefinitely, patients experience long-term eradication of normal B-cells and require monthly infusions of immunoglobulins. One more limitation of CAR T cell therapy is that T-cells are modified using lentiviral vectors, which, though acceptably safe, they are not free of oncogenic insertional mutagenesis risk and cleaner approaches would be desirable. mRNA transfections are used as a tool for protein overexpression that involves no risks of insertional mutagenesis and is expressed only transiently. However, mRNA is easily degraded inside the cell and protein levels quickly decline after 24-48h, requiring repeated boost of fresh mRNA. Moreover, current methods for mRNA delivery, especially lipofectamine or electroporation, are quite toxic to the cell, when they cross the cell membrane. We propose to bind the mRNA to gold nanoparticles (NP) functionalized with amine terminated groups as a safer way to target the cytosol via endocytosis. More importantly, we will induce a slow release of the mRNA inside the cell, therefore extending the mRNA half-life and protein expression. Gold NPs are of special interest for genetic material delivery due to their biocompatibility, tuneable surface chemistry where a combination of therapeutic and targeting moieties can be loaded, and their special optical and electronic properties that allow fine monitoring of the evolution, distribution and modifications of their chemical environment. Therefore, they seem ideal candidates for safe transport and slow release of mRNA.
Website visit project website
Network EuroNanoMed III
Call Joint Transnational Call (2018)

Project partner

Number Name Role Country
1 Catalan Institute of Nanoscience and Nanotecnology Coordinator Spain
2 Hospital Clínic de Barcelona Partner Spain
3 IRCCS-Istituto di Ricerche Farmacologiche “Mario Negri” Partner Italy
4 Tel Aviv University, Sackler School of Medicine Partner Israel
5 Applied Nanoparticles Partner Spain