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@ARTICLE{Reindl:302815,
      author       = {L. M. Reindl and L. Jalili and T. Bexte$^*$ and S.
                      Harenkamp and S. Thul and S. Hehlgans and A. Wallenwein and
                      F. Rothweiler and J. Cinatl and M. Michaelis and H. Bonig
                      and E. Gradhand and M. Vogler$^*$ and F. Rödel$^*$ and W.
                      S. Wels$^*$ and E. Ullrich$^*$},
      title        = {{P}recision targeting of rhabdomyosarcoma by combining
                      primary {CAR} {NK} cells and radiotherapy.},
      journal      = {Journal for ImmunoTherapy of Cancer},
      volume       = {13},
      number       = {7},
      issn         = {2051-1426},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2025-01355},
      pages        = {e011330},
      year         = {2025},
      abstract     = {Background: Rhabdomyosarcoma (RMS) is the most common type
                      of soft-tissue sarcoma in children, and it remains a
                      challenging cancer with poor outcomes in high-risk and
                      metastatic patients. This study reports the use of epidermal
                      growth factor receptor (EGFR)-targeted chimeric antigen
                      receptor (CAR) natural killer (NK) cells in combination with
                      radiotherapy as a novel immunotherapeutic approach for RMS
                      treatment.Methods: Primary human NK cells from healthy
                      donors were engineered using lentiviral transduction to
                      express a cetuximab-based EGFR-specific CAR. The ability of
                      the engineered NK cells to lyse RMS cells was then assessed
                      in vitro in RMS monolayers and spheroids, as well as against
                      chemotherapy-resistant and primary patient-derived RMS
                      cells. Migratory properties of NK cells were observed in a
                      subcutaneous RMS xenograft model using in vivo imaging, and
                      the efficacy of EGFR-CAR NK cells in combination with
                      localized fractionated radiotherapy was analyzed.Results:
                      Primary human EGFR-CAR NK cells demonstrated enhanced
                      cytotoxicity against multiple RMS cell lines in both
                      two-dimensional culture and three-dimensional spheroid
                      models. Furthermore, EGFR-CAR NK cells were highly efficient
                      against chemotherapy-resistant RMS cells and patient-derived
                      samples. Importantly, EGFR-CAR NK cells also exhibited
                      improved tumor homing compared with non-transduced NK cells
                      in an in vivo RMS xenograft model. Notably, the combination
                      of EGFR-CAR NK cell therapy with fractionated radiotherapy
                      further enhanced NK cell infiltration into the tumor and
                      reduced tumor growth.Conclusion: This study provides a
                      proof-of-concept for EGFR-CAR NK cells as a promising
                      immunotherapy for RMS, particularly when combined with
                      radiotherapy to overcome barriers of solid tumors. This
                      combinatorial approach may hold potential to improve
                      outcomes for patients with RMS and other EGFR-expressing
                      malignancies.},
      keywords     = {Humans / Animals / Rhabdomyosarcoma: therapy /
                      Rhabdomyosarcoma: immunology / Rhabdomyosarcoma:
                      radiotherapy / Rhabdomyosarcoma: pathology / Killer Cells,
                      Natural: immunology / Killer Cells, Natural: metabolism /
                      Killer Cells, Natural: transplantation / Mice / Receptors,
                      Chimeric Antigen: metabolism / Immunotherapy, Adoptive:
                      methods / Xenograft Model Antitumor Assays / Cell Line,
                      Tumor / ErbB Receptors: metabolism / Female / Chimeric
                      antigen receptor - CAR (Other) / Immunotherapy (Other) /
                      Natural killer - NK (Other) /
                      Radiotherapy/radioimmunotherapy (Other) / Solid tumor
                      (Other) / Receptors, Chimeric Antigen (NLM Chemicals) / ErbB
                      Receptors (NLM Chemicals)},
      cin          = {FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40623716},
      pmc          = {pmc:PMC12232460},
      doi          = {10.1136/jitc-2024-011330},
      url          = {https://inrepo02.dkfz.de/record/302815},
}