Th184 - Tackling Post-transplant Lymphoproliferative Disease - A New Model of Patient Derived Lung Organoids with Epstein-barr-virus Transformed B Cells as Test Platform for Epstein-barr-virus Specific T Cell Fighters

Dr. Lukas Ehlen – Berlin Institute of Health (BIH) Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany; Niklas Wiese – Berlin Center for Advanced Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany; Ugarit Daher – Berlin Institute of Health (BIH) Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany; Janine Arndt – Berlin Institute of Health (BIH) Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany; Dr. Andy Römhild – Berlin Center for Advanced Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany; Prof. Dr. Hans-Dieter Volk – Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Prof. Dr. Petra Reinke – Berlin Center for Advanced Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany; Dr. Michael Schmueck-Henneresse – Berlin Institute of Health (BIH) Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany; Dr. Leila Amini – Berlin Center for Advanced Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health (BIH) Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany

Abstract Text: Immunosuppressed patients after solid organ transplantation (SOT) are at high risk to develop malignancies. Post-transplant lymphoproliferative disease (PTLD) is one of the most severe complications after SOT, which manifests in the lung in up to 20% of the cases and treatment usually involves highly toxic agents.
Anti-viral adoptive T cell therapy represents a novel probably less toxic therapeutical approach, which has shown promising results among other indications also for PTLD. However, to confirm the safety and efficacy of these EBV-specific T-cell products as a basis for clinical translation, we are in urgent need of a suitable test platform.
We had the unique chance to set up a human co-culture platform of patient derived 3D lung organoids and patient derived EBV-transformed lymphoblastoid cells (LCLs) mimicking PTLD in the lung, as we have access to primary lung tissue and blood samples from the same patient. In order to generate this platform, we already implemented a co-culture of primary lung organoids and corresponding LCLs. We have found a suitable co-culture medium and investigated LCL interaction and infiltration into the organoid. Patient-specific EBV-reactive T cell product manufacturing is already established in a GMP compatible manner, and we are now integrating the antiviral T cell products into the PTLD platform for testing safety, efficacy and potential off-target activity. This autologous, human-derived platform holds the potential to yield valuable preclinical data regarding functionality and safety of human EBV-specific T cell products and will pave the way for clinical trials using EBV-specific T cell products.