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.
PRINCIPAL INVESTIGATOR
Laboratory Tumorgenetics and Immunology
TRIO Research Center
University of Cologne
Robert-Koch-Straße 21
50931 Cologne
Department I of Internal Medicine
University Hospital of Cologne
Kerpener Straße 62
50937 Cologne
TRIO Research Center
University of Cologne
Robert-Koch-Straße 21
50931 Cologne
Project Interactions
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A01
Using autochthonous mouse models of aggressive lymphoma to systematically distill actionable vulnerabilities
Prof. Dr. med. Hans Christian Reinhardt -
B01
LYN kinase as a key regulator in the microenvironmental niche of B cell lymphoid tumors
Prof. Dr. med. Michael Hallek, Dr. rer. nat. Phuong-Hien Nguyen -
B02
Deciphering the role of BIRC3 in lymphomagenesis and resistance to therapy
Dr. rer. nat. Nieves Peltzer, Prof. Dr. med. Christian Pallasch -
C05
Characterization of Richter-transformed lymphoma and genomic instability as a potential vulnerability in 17p-deleted lymphomas
Prof. Dr. med. Björn Chapuy, Prof. Dr. med. Barbara Eichhorst