P26
Bypassing ex vivo CAR T cell manufacturing: leveraging LNPs for in vivo delivery
E Cetin(1) J Freitag(2) N von Auw(1) P Warncke(1,3) T E Papp(4) H Parhiz(4) U S Tretbar(1)
1:Department of Cell and Gene Therapy Development, Fraunhofer Institute of Cell Therapy and Immunology IZI, Leipzig, 04301, Germany; 2:Department of Diagnostic, Fraunhofer Institute of Cell Therapy and Immunology IZI, Leipzig, 04301, Germany; 3:Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, 09116, Germany; 4:Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, 19104, USA
Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a groundbreaking treatment for various cancers. Its applications are now spreading beyond oncology into areas such as autoimmune diseases. However, its widespread use is hindered by the current ex vivo production method, which is labor-intensive, logistically complex, time-consuming (2-7 weeks), and expensive with list prices approximately 320,000 EUR in Europe.
To address these challenges, our project explores mRNA-loaded lipid nanoparticles (LNPs) for in vivo CAR gene delivery to T cells. A key hurdle in this approach is enhancing specificity to T cells. We are engineering targeted LNPs (tLNPs) by conjugating T cell targeting molecules to functionalized lipids, aiming to achieve T-cell specificity through receptor-mediated endosomal uptake.
In vivo delivery has the potential to transform CAR T cell therapy into an off-the-shelf product, promoting its widespread use and accessibility across a broader range of diseases. Additionally, the transient expression of CARs would enable safer targeting of antigens previously excluded due to on-target-off-tumor toxicities, broadening the spectrum of treatable conditions and antigens.