CAR-NK Cells Targeting HER1 (EGFR) Show Efficient Anti-Tumor Activity against Head and Neck Squamous Cell Carcinoma (HNSCC).
Juliette Nowak, Marco Bentele, Ivana Kutle, Katharina Zimmermann, Jonathan Lukas Lühmann, Doris Steinemann, Stephan Kloess, Ulrike Koehl, Willi Roßberg, Amed Ahmed, Dirk Schaudien, Lavinia Neubert, Jan-Christopher Kamp, Mark P Kuehnel, Athanasia Warnecke, Axel Schambach, Michael Morgan
Author Information
Juliette Nowak: Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Marco Bentele: Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Ivana Kutle: Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Katharina Zimmermann: Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Jonathan Lukas Lühmann: Department of Human Genetics, Hannover Medical School, 30625 Hannover, Germany. ORCID
Doris Steinemann: Department of Human Genetics, Hannover Medical School, 30625 Hannover, Germany.
Stephan Kloess: Institute for Cellular Therapeutics, Hannover Medical School, 30625 Hannover, Germany.
Ulrike Koehl: Institute for Cellular Therapeutics, Hannover Medical School, 30625 Hannover, Germany.
Willi Roßberg: Department of Otolaryngology, Head and Neck Surgery, Hannover Medical School, 30625 Hannover, Germany.
Amed Ahmed: Department of Otolaryngology, Head and Neck Surgery, Hannover Medical School, 30625 Hannover, Germany.
Dirk Schaudien: Fraunhofer Institute for Toxicology and Experimental Medicine, ITEM, 30625 Hannover, Germany.
Lavinia Neubert: Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany.
Jan-Christopher Kamp: Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany. ORCID
Mark P Kuehnel: Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany.
Athanasia Warnecke: Department of Otolaryngology, Head and Neck Surgery, Hannover Medical School, 30625 Hannover, Germany. ORCID
Axel Schambach: Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Michael Morgan: Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
(1) Background: HNSCC is a highly heterogeneous and relapse-prone form of cancer. We aimed to expand the immunological tool kit against HNSCC by conducting a functional screen to generate chimeric antigen receptor (CAR)-NK-92 cells that target HER1/epidermal growth factor receptor (EGFR). (2) Methods: Selected CAR-NK-92 cell candidates were tested for enhanced reduction of target cells, CD107a expression and IFNγ secretion in different co-culture models. For representative HNSCC models, patient-derived primary HNSCC (pHNSCC) cell lines were generated by employing an EpCAM-sorting approach to eliminate the high percentage of non-malignant cells found. (3) Results: 2D and 3D spheroid co-culture experiments showed that anti-HER1 CAR-NK-92 cells effectively eliminated SCC cell lines and primary HNSCC (pHNSCC) cells. Co-culture of tumor models with anti-HER1 CAR-NK-92 cells led to enhanced degranulation and IFNγ secretion of NK-92 cells and apoptosis of target cells. Furthermore, remaining pHNSCC cells showed upregulated expression of putative cancer stem cell marker CD44v6. (4) Conclusions: These results highlight the promising potential of CAR-NK cell therapy in HNSCC and the likely necessity to target multiple tumor-associated antigens to reduce currently high relapse rates.
