The Department of Molecular and Translational Medicine at the University of Brescia (Italy) is seeking highly motivated candidates for a 1-year postdoctoral research fellowship (Assegno di Ricerca), starting by March 1, 2025. Join an innovative research team under the expert guidance of Prof. Paolo Bergese.
- Monthly stipend: €1,500
- Duration: 1 year, with a focus on cutting-edge molecular and translational research.
If you're passionate about advancing your research career in a dynamic academic environment, this is the perfect opportunity!
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Abstract of the research project:
Extracellular vesicles (EVs) are universal means of intercellular communication, used by cells to transfer lipids, proteins, and nucleic acids. These innate properties, along with biocompatibility and sustainability, make EVs strong candidates to become the next generation of mRNA delivery vehicles. The program aims to develop EV-based nanocarriers for mRNA delivery, to be employed in the experiments outlined in the project to which the program is connected (ORGANO-CAR: Advancing CAR-T Therapy through Organoid-Based Validation and Nanoparticle-Mediated mRNA Delivery). The focus will be on the top-down synthesis of EVs from red blood cells (RBC-EV) and their exogenous loading with a tumor-specific CAR-T mRNA (CAR-mRNA). If necessary, chemical modifications of RBC-EVs will be developed and employed (e.g., hybridizing them with liposomes or applying click chemistry techniques).
ORGANO-CAR: Advancing CAR-T Therapy through Organoid-Based Validation and Nanoparticle-Mediated mRNA Delivery)
Abstract. Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized hematological cancer treatment, yet its application to solid tumors faces challenges, including adverse reactions, uncertain long-term safety, and high costs. The ORGANO-CAR project seeks to redefine CAR-T therapy for solid tumors by integrating tumor organoids and advanced nanotechnology. In solid tumors, the complex interplay between the immune system and the tumor microenvironment poses challenges for CAR-T therapy. Nanotechnology provides precise mRNA delivery for CAR-T without traditional viral vectors, reducing off-target effects. Tumor organoids, three-dimensional in vitro cultures replicating native tumor environments, offer a transformative platform for CAR-T validation, maintaining genetic and phenotypic characteristics. The main objective is to develop and validate ORGANO-CAR, an integrated platform leveraging tumor organoids and nanotechnology for enhanced CAR-T therapy. Specific tasks include sample collection for the generation of tumor organoids through an already established protocol, CAR-T production and optimization, nanoparticle-mediated delivery of mRNA-encoding CAR, and comparative analysis of CAR-T function. ORGANO-CAR aligns with the grant proposal's focus on novel nanotechnology strategies for CAR-modified immune effectors. It integrates innovative technologies, emphasizing efficiency, safety, and persistent immune effectors, contributing to precision medicine. Anticipated impacts include transformative shifts in CAR-T therapy for solid tumors, with enhanced safety, efficacy, and a validated organoid-based platform. Insights gained from navigating the tumor microenvironment within 3D organoids aim to redefine standards of care. In summary, ORGANO- CAR represents a pioneering initiative at the intersection of nanotechnology, organoids, and CAR- T therapy, with the potential to reshape the landscape of immunotherapies for challenging solid tumors.