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

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1228894

DOI=10.3389/fimmu.2023.1228894

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>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. </p></sec><sec><title>Methods</title><p>Here, we assess the efficacy of clinically usable CAR-engineered NK cell line NK-92/5.28.z against ErbB2-positive RMS <italic>in vitro</italic> and in a metastatic xenograft mouse model.</p></sec><sec><title>Results</title><p>Our results show that NK-92/5.28.z cells effectively kill RMS cells <italic>in vitro</italic> 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.</p></sec><sec><title>Discussion</title><p>These findings encourage further development of NK-92/5.28.z cells as off-the-shelf immunotherapy for the treatment of metastatic RMS.</p></sec>