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Development and efficacy of a lipid nanocarrier loaded with mRNA intended for transient CAR-T response in acute lymphoblastic leukemia treatment

Grant number: 22/07303-8
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): February 15, 2023
Effective date (End): February 14, 2024
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Luciana Biagini Lopes
Grantee:Giovanna Cassone Salata
Supervisor: Molly Stevens
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Karolinska Institutet, Sweden  
Associated to the scholarship:19/26048-6 - Development and application of multifunctional nanocarriers for intraductal delivery of chemotherapy aiming at Breast Cancer treatment, BP.DR

Abstract

Acute lymphoblastic leukemia (ALL) represents 1 every 4 pediatric cancer and commonly affects lymphocyte B cells. The survival rate increased to almost 70% after the approval of Chimeric Antigen Receptor (CAR) T cell therapy, however the limitations for a wide-scale production, costs and severe adverse effects hinders its application. In this project, we propose the optimization and application in vivo of an affibody-decorated lipid nanoparticle (LNP) aiming a transient CAR-T therapy based on the delivery of CAR-encoding mRNA to CD8+ or CD4+ T cells. More specifically, we propose the functionalization of LNPs with affibodies engineered to recognize T cells and bind to a cluster of differentiation protein specifically expressed by T cells for efficient cell internalization. The LNP's uptake and trafficking in the T cells, release of the mRNA, cytotoxic and hemolytic effects will be studied, and the efficacy of the LNP will be validated in vivo. With this study, we aim to contribute to the development of a safer and affordable CAR-T therapy. (AU)

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