Enhancing GvL responses by donor-derived CAR-modified CD8+ T memory stem cells (A07)

• Subject Area: Hematology, Oncology ; Immunology ; Clinical Immunology and Allergology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 324392634

IL-10 is emerging as a critical Achilles´ heel limiting the functionality of donor-derived CD19-CAR CD8+ T memory stem cells (TSCM) in the treatment of B-cell malignancies relapsing after ASCT. In this project, we seek to elucidate the role of IL-10 in CAR TSCM cell biology and develop strategies to overcome IL-10-mediated immunosuppression. Specifically, we will engineer CAR TSCM with (i) dominant-negative IL-10 receptors, (ii) IL-10 switch receptors converting IL-10 immunosuppressive signaling into T-cell supportive signals, and (iii) synthetic intramembrane proteolysis receptors designed to sustain stemness in response to IL-10.

• 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. Luca Gattinoni; Privatdozent Dr. Dennis Harrer