TY  - JOUR
A1  - Gossel, Leonie D. H.
A1  - Heim, Catrin Birgit
A1  - Pfeffermann, Lisa-Marie
A1  - Moser, Laura M.
A1  - Bönig, Halvard-Björn
A1  - Klingebiel, Thomas
A1  - Bader, Peter
A1  - Wels, Winfried
A1  - Merker, Michael
A1  - Rettinger, Eva
T1  - Retargeting of NK-92 cells against high-risk rhabdomyosarcomas by means of an ERBB2 (HER2/Neu)-specific chimeric antigen receptor
T2  - Cancers
N2  - The dismal prognosis of pediatric and young adult patients with high-risk rhabdomyosarcoma (RMS) underscores the need for novel treatment options for this patient group. In previous studies, the tumor-associated surface antigen ERBB2 (HER2/neu) was identified as targetable in high-risk RMS. As a proof of concept, in this study, a novel treatment approach against RMS tumors using a genetically modified natural killer (NK)-92 cell line (NK-92/5.28.z) as an off-the-shelf ERBB2-chimeric antigen receptor (CAR)-engineered cell product was preclinically explored. In cytotoxicity assays, NK-92/5.28.z cells specifically recognized and efficiently eliminated RMS cell suspensions, tumor cell monolayers, and 3D tumor spheroids via the ERBB2-CAR even at effector-to-target ratios as low as 1:1. In contrast to unmodified parental NK-92 cells, which failed to lyse RMS cells, NK-92/5.28.z cells proliferated and became further activated through contact with ERBB2-positive tumor cells. Furthermore, high amounts of effector molecules, such as proinflammatory and antitumoral cytokines, were found in cocultures of NK-92/5.28.z cells with tumor cells. Taken together, our data suggest the enormous potential of this approach for improving the immunotherapy of treatment-resistant tumors, revealing the dual role of NK-92/5.28.z cells as CAR-targeted killers and modulators of endogenous adaptive immunity even in the inhibitory tumor microenvironment of high-risk RMS.
KW  - RMS
KW  - ERBB2
KW  - HER2/neu
KW  - NK-92
KW  - CAR
KW  - cancer immunotherapy
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62465
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-624650
SN  - 2072-6694
N1  - This  research  was  funded  by  the  LOEWE-FCI,  Frankfurt  Cancer  Institute,  Frankfurt am Main, Germany, funded by the Hessian Ministry of Higher Education, Research and the Arts(2019). This work was also supported by grants from the Else Kröner-Fresenius-Stiftung (to L.M.M.),grants from the Mildred-Scheel-Nachwuchszentrum (MNSZ), Frankfurt am Main, Germany (to E.R.,70113301), grants from the Parents Association “Hilfe für krebskranke-Kinder e.V.”, Frankfurt amMain, Germany, and unrestricted grants from Baker & McKenzie Partnerschaft von Rechtsanwältenund Steuerberatern mbB, Frankfurt am Main, Germany.
VL  - 13
IS  - 6, art. 1443
SP  - 1
EP  - 18
PB  - MDPI
CY  - Basel
ER  -