Jul
6
2022
Upcoming webinar

Transient expression of mRNA lipid nanoparticle-based chimeric antigen receptors for safe immunotherapy

Wednesday July 6th 2022 08:00 PDT / 11:00 EDT / 16:00 BST / 17:00 CEST
Sponsor
Transient expression of mRNA lipid nanoparticle-based chimeric antigen receptors for safe immunotherapy

Live30 webinars are thirty minute presentations designed to update you on the latest innovations, applications and data in a fast yet interactive format.

T cells engineered with chimeric antigen receptors (CARs) has shown great success in the treatment of selected hematologic malignancies. However, approved CAR T-cell therapies are produced in a patient-specific basis by viral transduction, which is not only time-consuming and costly, 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, 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. For both methods, CAR-mRNA was optimized in terms of stability and immunogenicity. CAR-T cells generated with mRNA-LNPs outperformed EP-based CAR-T cells in terms of 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.

  • CAR-expression is a matter of mRNA stability and immunogenicity
  • LNP-derived CAR-T cells outperform electroporated CAR-T cells in efficacy and persistency
  • LNP-derived CAR-T cells are comparable to virally transduced CAR-T cells in tumor lysis efficacy

Sandy Tretbar, PhD

Lead of Advanced Therapy Medicinal Products (ATMP) Engineering Unit, Fraunhofer IZI

Dr. Sandy Tretbar obtained her PhD in Molecular Biology at Leipzig University in Germany. She then pursued her first Postdoc in the field of RNA biochemistry and biophysics at the University of Wisconsin-Madison. Her second Postdoc was in an immunology lab at the Martin-Luther-Universität Halle-Wittenberg. She joined Fraunhofer Institute for Cell Therapy and Immunology IZI (Fraunhofer IZI) in 2018. Currently, she is the Group Leader of the Advanced Therapy Medicinal Products (ATMP) Engineering group. Her research experience is in the RNA field and currently works on cell therapy in immuno-oncology to investigate mRNA-based gene therapy and the production of ATMPs for the treatment of cancer and various other diseases.

8
Days

SPEAKERS

Sandy Tretbar
Sandy Tretbar
Lead of Advanced Therapy Medicinal Products (ATMP) Engineering Unit at Fraunhofer IZI

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