TY  - JOUR
A1  - Feigl, Frederik Fabian
A1  - Stahringer, Anika
A1  - Peindl, Matthias
A1  - Dandekar, Gudrun
A1  - Koehl, Ulrike
A1  - Fricke, Stephan
A1  - Schmiedel, Dominik
T1  - Efficient redirection of NK cells by genetic modification with chemokine receptors CCR4 and CCR2B
JF  - International Journal of Molecular Sciences
N2  - Natural killer (NK) cells are a subset of lymphocytes that offer great potential for cancer immunotherapy due to their natural anti-tumor activity and the possibility to safely transplant cells from healthy donors to patients in a clinical setting. However, the efficacy of cell-based immunotherapies using both T and NK cells is often limited by a poor infiltration of immune cells into solid tumors. Importantly, regulatory immune cell subsets are frequently recruited to tumor sites. In this study, we overexpressed two chemokine receptors, CCR4 and CCR2B, that are naturally found on T regulatory cells and tumor-resident monocytes, respectively, on NK cells. Using the NK cell line NK-92 as well as primary NK cells from peripheral blood, we show that genetically engineered NK cells can be efficiently redirected using chemokine receptors from different immune cell lineages and migrate towards chemokines such as CCL22 or CCL2, without impairing the natural effector functions. This approach has the potential to enhance the therapeutic effect of immunotherapies in solid tumors by directing genetically engineered donor NK cells to tumor sites. As a future therapeutic option, the natural anti-tumor activity of NK cells at the tumor sites can be increased by co-expression of chemokine receptors with chimeric antigen receptors (CAR) or T cell receptors (TCR) on NK cells can be performed in the future.
KW  - chemokine receptor
KW  - migration
KW  - immune cell infiltration
KW  - trafficking
KW  - NK cells
KW  - immunotherapy
KW  - CCR2
KW  - CCR4
KW  - genetic engineering
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304049
SN  - 1422-0067
VL  - 24
IS  - 4
ER  -