Frontiers in Immunology (Aug 2023)

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

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

DOI
https://doi.org/10.3389/fimmu.2023.1228894
Journal volume & issue
Vol. 14

Abstract

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IntroductionMetastatic 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. MethodsHere, 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.ResultsOur 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.DiscussionThese findings encourage further development of NK-92/5.28.z cells as off-the-shelf immunotherapy for the treatment of metastatic RMS.

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