Advanced CAR T cell engineering to augment the GvL effect of ASCT (A03)

• Subject Area: Hematology, Oncology ; Immunology ; Clinical Immunology and Allergology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 324392634

We have developed CAR-T cells as 'bridge to transplant' (pre-ASCT) or as 'CAR donor lymphocyte infusion' (post-ASCT) in AML and multiple myeloma. Here, we will investigate the effect of glucocorticoids on CAR-T cells and render them resistant through gene-editing to maintain anti-tumor functionality during GvHD and/or CRS (Aim 1); we will accomplish serial antigen targeting for enhanced GvL effect (Aim 2); and we will analyze how alloreactivity and inflammation may cause AML resistance and/or neurotoxicity during CAR-T cell therapy (Aim 3) to improve the outcome of ASCT and integrate CAR-T therapy into the treatment algorithm.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 221: Modulation of graft-versus-host and graft-versus-leukemia immune responses after allogeneic stem cell transplantation
• Applicant Institution: Universität Regensburg
• Project Heads: Dr. Sophia Danhof, since 1/2026; Professor Dr. Hermann Einsele; Professor Dr. Michael Hudecek