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

Autor:	Heim C; Goethe University Frankfurt, Department of Pediatrics, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Frankfurt am Main, Germany., Moser LM; Goethe University Frankfurt, Department of Pediatrics, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Frankfurt am Main, Germany.; German Cancer Consortium (DKTK), Partner Site Frankfurt am Main, a Partnership Between DKFZ, University Hospital and Georg-Speyer-Haus, Frankfurt am Main, Germany.; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany.; Universitäres Centrum für Tumorerkrankungen (UCT), Frankfurt am Main, Germany., Kreyenberg H; Goethe University Frankfurt, Department of Pediatrics, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Frankfurt am Main, Germany., Bonig HB; Department of Cellular Therapeutics/Cell Processing, Institute for Transfusion Medicine and Immunotherapy, Goethe University, Frankfurt am Main, Germany.; Division of Hematology, Department of Medicine, University of Washington, Seattle, WA, United States., Tonn T; Experimental Transfusion Medicine, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, Dresden, Germany., Wels WS; German Cancer Consortium (DKTK), Partner Site Frankfurt am Main, a Partnership Between DKFZ, University Hospital and Georg-Speyer-Haus, Frankfurt am Main, Germany.; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany.; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany., Gradhand E; Universitäres Centrum für Tumorerkrankungen (UCT), Frankfurt am Main, Germany.; Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany., Ullrich E; German Cancer Consortium (DKTK), Partner Site Frankfurt am Main, a Partnership Between DKFZ, University Hospital and Georg-Speyer-Haus, Frankfurt am Main, Germany.; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany.; Universitäres Centrum für Tumorerkrankungen (UCT), Frankfurt am Main, Germany.; Experimental Immunology, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt, Germany., Meister MT; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.; Oncode Institute, Utrecht, Netherlands., Koerkamp MG; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.; Oncode Institute, Utrecht, Netherlands., Holstege FCP; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.; Center for Molecular Medicine, UMC Utrecht and Utrecht University, Utrecht, Netherlands., Drost J; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.; Oncode Institute, Utrecht, Netherlands., Klusmann JH; German Cancer Consortium (DKTK), Partner Site Frankfurt am Main, a Partnership Between DKFZ, University Hospital and Georg-Speyer-Haus, Frankfurt am Main, Germany.; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany.; Universitäres Centrum für Tumorerkrankungen (UCT), Frankfurt am Main, Germany.; Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany., Bader P; Goethe University Frankfurt, Department of Pediatrics, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Frankfurt am Main, Germany.; Universitäres Centrum für Tumorerkrankungen (UCT), Frankfurt am Main, Germany., Merker M; Goethe University Frankfurt, Department of Pediatrics, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Frankfurt am Main, Germany.; Universitäres Centrum für Tumorerkrankungen (UCT), Frankfurt am Main, Germany., Rettinger E; Goethe University Frankfurt, Department of Pediatrics, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Frankfurt am Main, Germany.; German Cancer Consortium (DKTK), Partner Site Frankfurt am Main, a Partnership Between DKFZ, University Hospital and Georg-Speyer-Haus, Frankfurt am Main, Germany.; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany.; Universitäres Centrum für Tumorerkrankungen (UCT), Frankfurt am Main, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Aug 18; Vol. 14, pp. 1228894. Date of Electronic Publication: 2023 Aug 18 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1228894
Abstrakt:	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. Competing Interests: J-HK has advisory roles for Bluebird Bio, Novartis, Roche and Jazz Pharmaceuticals. TT and WW are named as inventors on patents and patent applications related to the study therapeutic owned by their respective academic institutions. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. (Copyright © 2023 Heim, Moser, Kreyenberg, Bonig, Tonn, Wels, Gradhand, Ullrich, Meister, Koerkamp, Holstege, Drost, Klusmann, Bader, Merker and Rettinger.)
Databáze:	MEDLINE
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