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P24

CAR-T cells: a new strategy to fight cytomegalovirus infections in the immunocompromised host

 

S Kübel(1) C Bednar(1) M Thomas(1) T Winkler(2) A Ensser(1)

1:Virology, University Hospital Erlangen, Erlangen, 91054, Germany; 2:Genetics, Friedrich-Alexander-University, Erlangen, 91054, Germany

Even today, human cytomegalovirus (CMV) infection or reactivation remains a life-threatening complication for immunocompromised patients, especially in stem cell transplant recipients. Inspired by cancer immunotherapy, we aim to establish and functionally investigate CMV-specific chimeric antigen receptor (CAR)-T cells, with the goal of effective in vitro and in vivo CMV control. CMV glycoproteins are displayed on the surface of infected cells during the viral replication cycle. Here, multiple CAR constructs recognizing glycoproteins of murine CMV (MCMV) have been engineered in our group and MCMV-specific murine CAR-T cells are currently produced by retroviral transduction. Binding of a specific CAR-T cell to its (viral) antigen directly initiates T cell effector functions, via intracellular signalling domains of a T cell receptor. By performing in vitro killing assays, using two MCMV glycoprotein expressing reporter cell lines (Nano-luciferase, CRSTAL), we could proof antigen specific recognition by and activation of our murine CAR-T cells as well as granzyme B mediated cytotoxicity and target cell lysis. Currently, our CAR-T cells are investigated using MCMV infected murine fibroblasts. Initial results indicate weak direct lysis of infected cells but strong reduction of viral spread. In near future, a proof-of-principle in vivo study will be conducted in an established MCMV challenge model.

Sekretariat der DG-GT e.V.
Institut für Experimentelle Hämatologie
Hildegard Büning
Carl-Neuberg-Str. 1
30625 Hannover

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