Register for the upcoming Teatime Webinar

 

Please fill out this form to register for the upcoming PNI Teatime Webinar Series: Transient Expression of mRNA-LNP-based Chimeric Antigen Receptors for Safe Immunotherapy, presented by Reni Kitte, MSc., Research associate at Fraunhofer IZI.

 

Date: Wednesday, August 24

Time: 2:30pm GMT+1 | 3:30pm CEST

 

 

Abstract

 

Engineered T cells expressing chimeric antigen receptors (CARs) have proven as efficacious therapy against selected B cell malignancies. However, approved CAR T cell therapies are produced on a patient-specific basis by viral transduction, which is not only time- and cost-intensive, but may also pose safety issues. Therefore, transfer of in vitro-transcribed (IVT) CAR-encoding mRNA into T cells is being pursued as a promising and safe alternative to viral and non-viral DNA-based gene modification.  In this context, the CAR-mRNA was optimized in terms of stability and immunogenicity. Lipid nanoparticle (LNP)-based transfer of CAR-mRNA directly into T cells was compared with electroporation (EP), currently the state-of-the-art method for transient transfection used in clinical trials. CAR T cells generated with mRNA-LNPs outperformed EP-based CAR T cells regarding efficacy and persistence in vitro. Moreover, transient transfection of T cells with CAR-encoding mRNA-LNPs resulted in a CAR expression and lysis of tumor cells comparable to virally transduced CAR T cells in vitro. 

 

Our data provide a good explanation for the poor performance of EP-derived transient CAR T cells used in current clinical trials and highlight mRNA-LNP-derived CAR T cells as a next-generation transient approach for clinical trials.