ErbB2 (HER2)-CAR-NK-92 cells for enhanced immunotherapy of metastatic fusion-driven alveolar rhabdomyosarcoma

Catrin Heim, Laura M Moser, Herman Kreyenberg, Halvard B Bonig, Torsten Tonn, Winfried S Wels, Elise Gradhand, Evelyn Ullrich, Michael T Meister, Marian Groot Koerkamp, Frank C P Holstege, Jarno Drost, Jan-Henning Klusmann, Peter Bader, Michael Merker, Eva Rettinger

Research output: Contribution to journalArticlepeer-review

Abstract

INTRODUCTION: Metastatic rhabdomyosarcoma (RMS) is a challenging tumor entity that evades conventional treatments and endogenous antitumor immune responses, highlighting the need for novel therapeutic strategies. Applying chimeric antigen receptor (CAR) technology to natural killer (NK) cells may offer safe, effective, and affordable therapies that enhance cancer immune surveillance.

METHODS: Here, we assess the efficacy of clinically usable CAR-engineered NK cell line NK-92/5.28.z against ErbB2-positive RMS in vitro and in a metastatic xenograft mouse model.

RESULTS: Our results show that NK-92/5.28.z cells effectively kill RMS cells in vitro and significantly prolong survival and inhibit tumor progression in mice. The persistence of NK-92/5.28.z cells at tumor sites demonstrates efficient antitumor response, which could help overcome current obstacles in the treatment of solid tumors.

DISCUSSION: These findings encourage further development of NK-92/5.28.z cells as off-the-shelf immunotherapy for the treatment of metastatic RMS.

Original languageEnglish
Pages (from-to)1228894
JournalFrontiers in immunology
Volume14
DOIs
Publication statusPublished - 2023

Keywords

  • Humans
  • Animals
  • Mice
  • Rhabdomyosarcoma, Alveolar/therapy
  • Receptors, Chimeric Antigen/genetics
  • Immunotherapy
  • Rhabdomyosarcoma/therapy
  • Disease Models, Animal
  • Killer Cells, Natural
  • Neoplasms, Second Primary

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