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

doi:10.3389/fimmu.2023.1228894

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

Group Drost

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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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.

Originele taal-2	Engels
Pagina's (van-tot)	1228894
Tijdschrift	Frontiers in immunology
Volume	14
DOI's	https://doi.org/10.3389/fimmu.2023.1228894
Status	Gepubliceerd - 2023

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10.3389/fimmu.2023.1228894

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Heim, C., Moser, L. M., Kreyenberg, H., Bonig, H. B., Tonn, T., Wels, W. S., Gradhand, E., Ullrich, E., Meister, M. T., Koerkamp, M. G., Holstege, F. C. P., Drost, J., Klusmann, J.-H., Bader, P., Merker, M., & Rettinger, E. (2023). ErbB2 (HER2)-CAR-NK-92 cells for enhanced immunotherapy of metastatic fusion-driven alveolar rhabdomyosarcoma. Frontiers in immunology, 14, 1228894. https://doi.org/10.3389/fimmu.2023.1228894

@article{b654d74fe7f840d193f4ebfc722a2ca9,

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

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.",

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

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

note = "Copyright {\textcopyright} 2023 Heim, Moser, Kreyenberg, Bonig, Tonn, Wels, Gradhand, Ullrich, Meister, Koerkamp, Holstege, Drost, Klusmann, Bader, Merker and Rettinger.",

year = "2023",

doi = "10.3389/fimmu.2023.1228894",

language = "English",

volume = "14",

pages = "1228894",

journal = "Frontiers in immunology",

issn = "1664-3224",

publisher = "Frontiers Media S.A.",

}

Heim, C, Moser, LM, Kreyenberg, H, Bonig, HB, Tonn, T, Wels, WS, Gradhand, E, Ullrich, E, Meister, MT, Koerkamp, MG, Holstege, FCP, Drost, J, Klusmann, J-H, Bader, P, Merker, M & Rettinger, E 2023, 'ErbB2 (HER2)-CAR-NK-92 cells for enhanced immunotherapy of metastatic fusion-driven alveolar rhabdomyosarcoma', Frontiers in immunology, vol. 14, blz. 1228894. https://doi.org/10.3389/fimmu.2023.1228894

TY - JOUR

T1 - ErbB2 (HER2)-CAR-NK-92 cells for enhanced immunotherapy of metastatic fusion-driven alveolar rhabdomyosarcoma

AU - Heim, Catrin

AU - Moser, Laura M

AU - Kreyenberg, Herman

AU - Bonig, Halvard B

AU - Tonn, Torsten

AU - Wels, Winfried S

AU - Gradhand, Elise

AU - Ullrich, Evelyn

AU - Meister, Michael T

AU - Koerkamp, Marian Groot

AU - Holstege, Frank C P

AU - Drost, Jarno

AU - Klusmann, Jan-Henning

AU - Bader, Peter

AU - Merker, Michael

AU - Rettinger, Eva

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Humans

KW - Animals

KW - Mice

KW - Rhabdomyosarcoma, Alveolar/therapy

KW - Receptors, Chimeric Antigen/genetics

KW - Immunotherapy

KW - Rhabdomyosarcoma/therapy

KW - Disease Models, Animal

KW - Killer Cells, Natural

KW - Neoplasms, Second Primary

U2 - 10.3389/fimmu.2023.1228894

DO - 10.3389/fimmu.2023.1228894

M3 - Article

C2 - 37662907

SN - 1664-3224

VL - 14

SP - 1228894

JO - Frontiers in immunology

JF - Frontiers in immunology

ER -

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

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