Novel Non-Viral DNA-based Gene Therapy Vector for CAR T Engineering In Vivo скачать в хорошем качестве

Novel Non-Viral DNA-based Gene Therapy Vector for CAR T Engineering In Vivo

The development of immune cells engineered to express Chimeric Antigen Receptors (CARs) has transformed cancer therapy. Ex vivo CAR-T cell treatments have achieved notable clinical and commercial success. However, they are also associated with significant limitations, including high costs, complex and time-consuming manufacturing, potential toxicities, and logistical challenges tied to patient-specific cell production. These barriers underscore the urgent need for next-generation approaches that can enhance accessibility, reduce complexity, and improve overall treatment efficiency. We present an innovative cell-targeted lipid nanoparticle (tLNP) platform designed to deliver both DNA and RNA directly to T cells, enabling in situ CAR-T cell generation. This tLNP system consists of lipid nanoparticles carrying transposon DNA (encoding CAR), mRNA (encoding transposase), and targeting/activating protein components. We demonstrate that this approach can activate resting primary T cells and facilitate stable CAR expression without requiring traditional ex vivo expansion or external activation steps. Beyond in vitro modification, we show that this non-viral vector drives functional CAR-T cell generation in vivo. We would like to present and discuss our latest data demonstrating successful generation of CAR T in an NSG mouse model injected with a human B-cell leukemia cell line. We will discuss that a single dose of tLNP (carrying DNA/RNA) results in durable CAR-T cell generation, tumor control, and prolonged survival. Furthermore, we will present a biodistribution analysis based on whole-organ imaging, using fluorescence imaging of the Cy5.5 label alongside bioluminescence imaging (BLI) of luciferase mRNA and CAR–luciferase minicircle DNA (mcDNA). By transitioning CAR-T engineering from a labour-intensive, facility-based process to a simplified in vivo approach, this platform offers the potential to address key challenges in cell therapy—enhancing scalability, reducing costs, and increasing accessibility of CAR-T treatments. Speaker: Jacek Lubelski, Chief Technology Officer | Nanocell Therapeutics Visit Our Website for More Information on LNP Purification and Characterization: https://www.biaseparations.com/soluti... Get in Touch: Webpage: https://www.biaseparations.com E-mail: sales@biaseparations.com Tech support: Help.Bia@Sartorius.com