New strategies to improve the efficiency and safety of CAR-T cells for the treatment of B cell lymphoma (B05)

• Subject Area: Immunology ; Hematology, Oncology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 455784452

Chimeric antigen receptor (CAR) T cells remain one of the most advanced and promising forms of adoptive T-cell immunotherapy. However, the majority of patients with refractory B cell malignancies relapse after CAR T-cell treatment. Our preliminary data show that relapse upon CD19-specific CAR T cell therapy in patients with DLBCL is associated with increased expression of the immune checkpoint ligand CD80 on refractory DLBCL cells potentially leading to inhibition of CAR T cells function by CTLA-4 engagement. To disable this and other immune checkpoint-dependent negative mechanisms of T cell regulation, we have developed a new strategy based on the co-expression of chimeric checkpoint receptors (CCR) on CAR T cells. We will evaluate efficacy and persistence of CAR/CCR T cells in autochthonous mouse models and autologous humanized PDX mouse model of aggressive lymphoma.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1530: Elucidation and targeting of pathogenic mechanisms in B cell malignancies
• Applicant Institution: Universität zu Köln
• Project Heads: Dr. Markus Chmielewski; Professor Dr. Roland Tillmann Ullrich