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Exploring NKp44-CAR redirected T cells for adoptive immunotherapy

Laufzeit: 01.01.2020 - 31.12.2021

Kurzfassung


NKp44 is a member of the natural cytotoxicity receptor (NCR) family exclusively expressed on NK cells. Its ligand, a truncated form of the mixed-lineage leukemia-5 (MLL-5) protein (Nkp44-L), has been found to be expressed on numerous cancer cell lines and primary cancer specimen such as renal cell and bladder cell carcinomas (Baychelier et al., Blood 2013). Moreover, as anti-NKp44L monoclonal antibody strongly inhibit NK cell reactivity, NKp44 might be of interest to be deploited for exerting...NKp44 is a member of the natural cytotoxicity receptor (NCR) family exclusively expressed on NK cells. Its ligand, a truncated form of the mixed-lineage leukemia-5 (MLL-5) protein (Nkp44-L), has been found to be expressed on numerous cancer cell lines and primary cancer specimen such as renal cell and bladder cell carcinomas (Baychelier et al., Blood 2013). Moreover, as anti-NKp44L monoclonal antibody strongly inhibit NK cell reactivity, NKp44 might be of interest to be deploited for exerting antitumoral reactivity.
Thus, the goal of this project is to explore NKp44-CAR redirected T lymphocytes for antitumoral activity to different cancer cell lines and primary tumor cells. To this end, different NKp44-based 2nd generation CARs have been cloned and expressed on human T cells upon retroviral transduction. Different functional in vitro and subsequent in vivo studies will elucidate whether NKp44-CAR T cells can exert antitumor immunity that could be further exploited in CAR T cell based adoptive cellular therapy.
 
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