Disialoganglioside-specific human natural killer cells are effective against drug-resistant neuroblastoma

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Item Type:	Article
Title:	Disialoganglioside-specific human natural killer cells are effective against drug-resistant neuroblastoma
Creators Name:	Seidel, D., Shibina, A., Siebert, N., Wels, W.S., Reynolds, C.P., Huebener, N. and Lode, H.N.
Abstract:	The disialoganglioside GD2 is a well-established target antigen for passive immunotherapy in neuroblastoma (NB). Despite the recent success of passive immunotherapy with the anti-GD2 antibody ch14.18 and cytokines, treatment of high-risk NB remains challenging. We expanded the approach of GD2-specific, antibody-based immunotherapy to an application of a GD2-specific natural killer (NK) cell line, NK-92-scFv(ch14.18)-zeta. NK-92-scFv(ch14.18)-zeta is genetically engineered to express a GD2-specific chimeric antigen receptor generated from ch14.18. Here, we show that chimeric receptor expression enables NK-92-scFv(ch14.18)-zeta to effectively lyse GD2(+) NB cells also including partially or multidrug-resistant lines. Our data suggest that recognition of GD2 by the chimeric receptor is the primary mechanism involved in NK-92-scFv(ch14.18)-zeta-mediated lysis and is independent of activating NK cell receptor/ligand interactions. Furthermore, we demonstrate that NK-92-scFv(ch14.18)-zeta is able to mediate a significant anti-tumor response in vivo in a drug-resistant GD2(+) NB xenograft mouse model. NK-92-scFv(ch14.18)-zeta is an NB-specific NK cell line that has potential for future clinical development due to its high stability and activity toward GD2(+) NB cell lines.
Keywords:	Neuroblastoma GD2, Chimeric Antigen Receptor, Natural Killer Cell, Single-Chain Antibody
Source:	Cancer Immunology Immunotherapy
ISSN:	0340-7004
Publisher:	Springer
Volume:	64
Number:	5
Page Range:	621-634
Date:	May 2015
Official Publication:	https://doi.org/10.1007/s00262-015-1669-5
PubMed:	View item in PubMed

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