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Gossel LDH, Heim C, Pfeffermann LM, et al. Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor. Cancers (Basel). 2021;13(6)doi: 10.3390/cancers13061443.
Gossel, L. D. H., Heim, C., Pfeffermann, L. M., Moser, L. M., Bönig, H. B., Klingebiel, T. E., Bader, P., Wels, W. S., Merker, M., & Rettinger, E. (2021). Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor. Cancers, 13(6), . https://doi.org/10.3390/cancers13061443
Gossel, Leonie D H, et al. "Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor." Cancers vol. 13,6 (2021). doi: https://doi.org/10.3390/cancers13061443
Gossel LDH, Heim C, Pfeffermann LM, Moser LM, Bönig HB, Klingebiel TE, Bader P, Wels WS, Merker M, Rettinger E. Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor. Cancers (Basel). 2021 Mar 22;13(6). doi: 10.3390/cancers13061443. PMID: 33809981; PMCID: PMC8004684.
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Cancers (Basel). 2021 Mar 22;13(6). doi: 10.3390/cancers13061443.

Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor.

Cancers

Leonie D H Gossel, Catrin Heim, Lisa-Marie Pfeffermann, Laura M Moser, Halvard B Bönig, Thomas E Klingebiel, Peter Bader, Winfried S Wels, Michael Merker, Eva Rettinger

Affiliations

  1. Department for Children and Adolescents, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany.
  2. Department of Cellular Therapeutics/Cell Processing, Institute for Transfusion Medicine and Immunohematology Frankfurt am Main, Goethe University Medical School, 60528 Frankfurt am Main, Germany.
  3. German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, 60590 Frankfurt am Main, Germany.
  4. Frankfurt Cancer Institute (FCI), 60596 Frankfurt am Main, Germany.
  5. Universitäres Centrum für Tumorerkrankungen (UCT), 60590 Frankfurt am Main, Germany.
  6. Department of Medicine, Division of Hematology, University of Washington, Seattle, WA 98198-7720, USA.
  7. Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany.
  8. Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt am Main, Germany.

PMID: 33809981 PMCID: PMC8004684 DOI: 10.3390/cancers13061443

Abstract

The dismal prognosis of pediatric and young adult patients with high-risk rhabdomyosarcoma (RMS) underscores the need for novel treatment options for this patient group. In previous studies, the tumor-associated surface antigen ERBB2 (HER2/neu) was identified as targetable in high-risk RMS. As a proof of concept, in this study, a novel treatment approach against RMS tumors using a genetically modified natural killer (NK)-92 cell line (NK-92/5.28.z) as an off-the-shelf ERBB2-chimeric antigen receptor (CAR)-engineered cell product was preclinically explored. In cytotoxicity assays, NK-92/5.28.z cells specifically recognized and efficiently eliminated RMS cell suspensions, tumor cell monolayers, and 3D tumor spheroids via the ERBB2-CAR even at effector-to-target ratios as low as 1:1. In contrast to unmodified parental NK-92 cells, which failed to lyse RMS cells, NK-92/5.28.z cells proliferated and became further activated through contact with ERBB2-positive tumor cells. Furthermore, high amounts of effector molecules, such as proinflammatory and antitumoral cytokines, were found in cocultures of NK-92/5.28.z cells with tumor cells. Taken together, our data suggest the enormous potential of this approach for improving the immunotherapy of treatment-resistant tumors, revealing the dual role of NK-92/5.28.z cells as CAR-targeted killers and modulators of endogenous adaptive immunity even in the inhibitory tumor microenvironment of high-risk RMS.

Keywords: CAR; ERBB2; HER2/neu; NK-92; RMS; cancer immunotherapy

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