Frederik Fabian Feigl

Fraunhofer Institute for Cell Therapy and Immunology

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Dominik Schmiedel

Weizmann Institute of Science

F Gierschek

Goethe University Frankfurt

Stephan Fricke

Klinikum Chemnitz

Leon Buchinger

Goethe University Frankfurt

Ulrike Köhl

University Hospital Leipzig

Sabine Huenecke

Goethe University Frankfurt

Winfried S. Wels

Frankfurt Cancer Institute

Evelyn Ullrich

Goethe University Frankfurt

Gudrun Dandekar

Universitätsklinikum Würzburg

Maren Prüfer

Georg Speyer Haus

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Goethe University Frankfurt

University Hospital Frankfurt

Fraunhofer Institute for Cell Therapy and Immunology

Frankfurt Cancer Institute

University Hospital Leipzig

Leipzig University

Heidelberg University

German Cancer Research Center

Fraunhofer Research Institution for Materials Recycling and Resource Strategies IWKS

Georg Speyer Haus

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Empowering Natural Killer Cells to Combat Acute Myeloid Leukemia: Perspective on CAR-NK Cell Therapy

Transfusion Medicine and Hemotherapy (2024)

F Gierschek J Schlueter Ines Kühnel Frederik Fabian Feigl Dominik Schmiedel

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a high relapse rate and still limited therapeutic options. Natural killer (NK) cell-based immunotherapy has the potential to improve outcomes for patients with AML. Recent preclinical studies and early-stage clinical trials aim to enhance the intrinsic anti-leukemic properties of NK cells by selectively targeting AML cells with chimeric antigen receptors (CARs). Furthermore, NK and CAR-NK cells can be combined with other therapeutic modalities or engineered further to overcome the immunosuppressive microenvironment, and treatment resistance of AML blasts and leukemia-initiating cells (LIC). In this review, we summarize preclinical studies with cytokine-stimulated or genetically engineered NK cells derived from different cell sources for the treatment of AML and their translation into early-phase clinical trials. We also provide an overview of promising recent developments toward innovative NK cell-based therapies that may be implemented in the near future.

Cell therapy

10.1159/000540962

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Efficient Redirection of NK Cells by Genetic Modification with Chemokine Receptors CCR4 and CCR2B

International Journal of Molecular Sciences (2023)

Frederik Fabian Feigl Anika Stahringer Matthias Peindl Gudrun Dandekar Ulrike Koehl

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.

CCR4

Lymphokine-activated killer cell

CXCL14

NK-92

10.3390/ijms24043129

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