Benutzerspezifische Werkzeuge

Generation and characterization of armed natural killer cells for the immunotherapy of tumors

The aim of this research project is the development of genetically modified CAR-NK cells for immunotherapy of HER2/ErbB2-positive tumor cells.

Overexpression of the HER2/ErbB2 proto-oncogene is found in many tumor entities, such as breast cancer and gliomas.

Recent studies prove the efficiency of CAR-modified lymphocytes, but also show limitations of this approach. For example, an immunosuppressive tumor microenvironment or the induction of peripheral tolerance mechanisms can lead to inactivation of the immune effector cells used.

In particular, the expression of programmed death ligand 1 (PD-L1) on tumor tissue or associated tumor stroma inhibits an anti-tumor effect of activated T lymphocytes that have migrated into the tumor and of NK cells with expression of the PD-1 receptor.

Therefore, in addition to a ErbB2-specific CAR, an anti-PD-L1-CAR will be used in the project. This novel dual use of CARs in NK cells should overcome a PD-L1-influenced, immunosuppressive tumor microenvironment and significantly improve the anti-tumor efficacy of adoptive CAR-NK cell Transfer.

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