Efficacy and safety of HLA-DPB1-specific T cell receptors as mediators of graft-versus-leukemia effect (A02)

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

HLA-DPB1 mismatch antigens occur in allogeneic HSCT from unrelated donors and represent powerful leukemia rejections antigens. Here we develop allo-HLA-DPB1 specific chimeric antigen receptors (CAR-DP) that are genetically expressed in donor T cells to enhance the GvL effect. Special emphasis is placed on the prevention of treatment-induced HLA-DP-specific alloreactivity to non-hematopoietic tissues. For this we design a combinatorial ‘split CAR’ in which simultaneous binding to HLA-DP and a hematopoiesis-restricted antigen (e.g. CD45) is required to induce CAR T-cell activation. The split CAR system shall serve as a prototype for safe and effective adoptive T-cell therapy after allogeneic HSCT.

• 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; Professorin Dr. Simone Thomas