Efficacy and safety of HLA-DPB1-specific chimeric antigen receptors (CAR) as mediators of GvL effect (A02)

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

We developed a combinatorial ‘Logic-AND-Gating’ CAR that requires the simultaneous binding to alloHLA-DPB1 of patient origin and to the hematopoiesis-restricted antigen CD45 on leukemia cells for T cell activation. This new approach is thought to prevent HLA-DP-specific alloreactivity toward non-hematopoietic (CD45neg) tissues upon CAR treatment. We will now test this CAR and a novel alloHLA-A2/CD45 CAR for efficacy and toxicity in humanized NSG mouse models to show that this combinatorial ‘Logic-AND-gating’ CAR approach allows the induction of a selective GvL effect in the absence of GvHD.

• 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: Professor Dr. Wolfgang Herr; Dr. Patrick Schlegel, since 1/2026; Professorin Dr. Simone Thomas